CNS Neuroscience & Therapeutics最新文献_第6页

Olfactory bulb stimulation mitigates Alzheimer's-like disease progression 刺激嗅球可减轻阿尔茨海默氏症样疾病的进展

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-15 DOI: 10.1111/cns.70056

Morteza Salimi, Milad Nazari, Payam Shahsavar, Samaneh Dehghan, Mohammad Javan, Javad Mirnajafi-Zadeh, Mohammad Reza Raoufy

Background

Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits.

Aims

Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats.

Methods

Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing.

Results

OB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task.

Conclusion

This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.

背景大脑深部刺激（DBS）已被证明在缓解阿尔茨海默病（AD）方面具有潜力。然而，DBS 的侵入性为其应用带来了挑战。嗅球（OB）显示出与阿兹海默症相关的早期变化，并与记忆区域有广泛联系，为干预提供了一个有吸引力的切入点，有可能恢复恶化的记忆回路的正常活动。目的我们的研究考察了电刺激 OB 对淀粉样β（Aβ）AD 模型大鼠工作记忆的影响，以及 OB、内侧前额叶皮层、海马和内黑质的病理和电生理改变。方法雄性 Wistar 大鼠接受手术，在脑区植入电极，诱发类似阿尔茨海默病的疾病。对刺激组大鼠的双侧嗅球（OB）进行连续18天、每天1小时的电刺激，然后进行组织学、行为学和局部场电位信号处理评估。结果刺激外鼻刺激可抑制Aβ斑块的积累，并防止AD引起的工作记忆障碍。此外，在完成工作记忆任务时，它还能提高不同频段的功率，增强研究区域内的功能连接，尤其是伽马频段。结论这项临床前研究强调了基于嗅觉通路的脑刺激在调节深层记忆网络活动以治疗老年痴呆症方面的潜力。重要的是，通过鼻腔进入这一通路为开发针对嗅觉通路的微创方法奠定了基础。

{"title":"Olfactory bulb stimulation mitigates Alzheimer's-like disease progression","authors":"Morteza Salimi, Milad Nazari, Payam Shahsavar, Samaneh Dehghan, Mohammad Javan, Javad Mirnajafi-Zadeh, Mohammad Reza Raoufy","doi":"10.1111/cns.70056","DOIUrl":"https://doi.org/10.1111/cns.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deep brain stimulation (DBS) has demonstrated potential in mitigating Alzheimer's disease (AD). However, the invasive nature of DBS presents challenges for its application. The olfactory bulb (OB), showing early AD-related changes and extensive connections with memory regions, offers an attractive entry point for intervention, potentially restoring normal activity in deteriorating memory circuits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Our study examined the impact of electrically stimulating the OB on working memory as well as pathological and electrophysiological alterations in the OB, medial prefrontal cortex, hippocampus, and entorhinal cortex in amyloid beta (Aβ) AD model rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Wistar rats underwent surgery for electrode implantation in brain regions, inducing Alzheimer's-like disease. Bilateral olfactory bulb (OB) electrical stimulation was performed for 1 hour daily to the OB of stimulation group animals for 18 consecutive days, followed by the evaluations of histological, behavioral, and local field potential signal processing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>OB stimulation counteracted Aβ plaque accumulation and prevented AD-induced working memory impairments. Furthermore, it prompted an increase in power across diverse frequency bands and enhanced functional connectivity, particularly in the gamma band, within the investigated regions during a working memory task.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This preclinical investigation highlights the potential of olfactory pathway-based brain stimulation to modulate the activity of deep-seated memory networks for AD treatment. Importantly, the accessibility of this pathway via the nasal cavity lays the groundwork for the development of minimally invasive approaches targeting the olfactory pathway for brain modulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying modifiable factors associated with neuroimaging markers of brain health 确定与大脑健康神经影像标记相关的可改变因素

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-15 DOI: 10.1111/cns.70057

Liang-Yu Huang, Yan Fu, Yi Zhang, He-Ying Hu, Ling-Zhi Ma, Yi-Jun Ge, Yong-Li Zhao, Ya-Ru Zhang, Shi-Dong Chen, Jian-Feng Feng, Wei Cheng, Lan Tan, Jin-Tai Yu

Aims

Brain structural alterations begin long before the presentation of brain disorders; therefore, we aimed to systematically investigate a wide range of influencing factors on neuroimaging markers of brain health.

Methods

Utilizing data from 30,651 participants from the UK Biobank, we explored associations between 218 modifiable factors and neuroimaging markers of brain health. We conducted an exposome-wide association study using the least absolute shrinkage and selection operator (LASSO) technique. Restricted cubic splines (RCS) were further employed to estimate potential nonlinear correlations. Weighted standardized scores for neuroimaging markers were computed based on the estimates for individual factors. Finally, stratum-specific analyses were performed to examine differences in factors affecting brain health at different ages.

Results

The identified factors related to neuroimaging markers of brain health fell into six domains, including systematic diseases, lifestyle factors, personality traits, social support, anthropometric indicators, and biochemical markers. The explained variance percentage of neuroimaging markers by weighted standardized scores ranged from 0.5% to 7%. Notably, associations between systematic diseases and neuroimaging markers were stronger in older individuals than in younger ones.

Conclusion

This study identified a series of factors related to neuroimaging markers of brain health. Targeting the identified factors might help in formulating effective strategies for maintaining brain health.

目的大脑结构的改变早在出现脑部疾病之前就已经开始了；因此，我们旨在系统地研究大脑健康神经影像标志物的各种影响因素。方法我们利用英国生物库中 30651 名参与者的数据，探讨了 218 个可改变因素与脑健康神经影像标志物之间的关联。我们使用最小绝对收缩和选择算子（LASSO）技术进行了全暴露组关联研究。我们还进一步采用了限制性三次样条（RCS）来估计潜在的非线性相关性。根据单个因素的估计值计算神经影像标记物的加权标准化得分。最后，还进行了分层分析，以研究不同年龄段影响大脑健康的因素的差异。结果已确定的与脑健康神经影像标志物相关的因素分为六个领域，包括系统性疾病、生活方式因素、个性特征、社会支持、人体测量指标和生化标志物。加权标准化得分对神经影像标志物的解释方差百分比从 0.5% 到 7% 不等。值得注意的是，与年轻人相比，老年人的系统性疾病与神经影像标志物之间的关联性更强。结论本研究发现了一系列与脑健康神经影像标志物相关的因素。针对所发现的因素，可能有助于制定保持大脑健康的有效策略。

{"title":"Identifying modifiable factors associated with neuroimaging markers of brain health","authors":"Liang-Yu Huang, Yan Fu, Yi Zhang, He-Ying Hu, Ling-Zhi Ma, Yi-Jun Ge, Yong-Li Zhao, Ya-Ru Zhang, Shi-Dong Chen, Jian-Feng Feng, Wei Cheng, Lan Tan, Jin-Tai Yu","doi":"10.1111/cns.70057","DOIUrl":"https://doi.org/10.1111/cns.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Brain structural alterations begin long before the presentation of brain disorders; therefore, we aimed to systematically investigate a wide range of influencing factors on neuroimaging markers of brain health.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing data from 30,651 participants from the UK Biobank, we explored associations between 218 modifiable factors and neuroimaging markers of brain health. We conducted an exposome-wide association study using the least absolute shrinkage and selection operator (LASSO) technique. Restricted cubic splines (RCS) were further employed to estimate potential nonlinear correlations. Weighted standardized scores for neuroimaging markers were computed based on the estimates for individual factors. Finally, stratum-specific analyses were performed to examine differences in factors affecting brain health at different ages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The identified factors related to neuroimaging markers of brain health fell into six domains, including systematic diseases, lifestyle factors, personality traits, social support, anthropometric indicators, and biochemical markers. The explained variance percentage of neuroimaging markers by weighted standardized scores ranged from 0.5% to 7%. Notably, associations between systematic diseases and neuroimaging markers were stronger in older individuals than in younger ones.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identified a series of factors related to neuroimaging markers of brain health. Targeting the identified factors might help in formulating effective strategies for maintaining brain health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons GLS2 通过影响小鼠海马神经元的有丝分裂功能减少癫痫的发生

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-15 DOI: 10.1111/cns.70036

Yuan Gao, Limin Ma, Jinxian Yuan, Yunyi Huang, Yuenan Ban, Peng Zhang, Dandan Tan, Minxue Liang, Zhipeng Li, Chen Gong, Tao Xu, Xiaolan Yang, Yangmei Chen

Background

Altered mitophagy has been observed in various neurological disorders, such as epilepsy. The role of mitophagy in causing neuronal damage during epileptic episodes is significant, and recent research has indicated that GLS2 plays a crucial role in regulating autophagy. However, exactly how GLS2 affects epilepsy is still unclear.

Aims

To investigate the expression and distribution characteristics of GLS2 in epilepsy, and then observed the changes in behavior and electrophysiology caused by overexpression of GLS2 in epileptic mice, and determined whether GLS2 regulated seizure-like changes in the mouse model through the protective mechanism of mitophagy.

Results

The expression of GLS2 in a kainic acid (KA)-induced epileptic mouse model and aglutamate-inducedneuronal excitatory damage in HT22 cells model was downregulation. In brief, overexpression of GLS2 can alleviate epileptic activity. Subsequently, we demonstrated that GLS2 interacts with mitophagy-related proteins in a KA-induced epilepsy mouse model. Mechanistically, overexpression of GLS2 inhibited mitophagy in epileptic mice, downregulating the expression of LC3 and reducing ROS production.

Conclusions

This study proves the GLS2 expression pattern is abnormal in epileptic mice. The function of mitophagy in hippocampal neurons is affected by GLS2, and overexpression of GLS2 can reduce the occurrence of seizure-like events (SLEs) by altering mitophagy function. Thus, GLS2 might control seizures, and our findings provide a fresh avenue for antiepileptic treatment and offer novel insights into treating and preventing epilepsy.

背景在癫痫等多种神经系统疾病中观察到有丝分裂改变。在癫痫发作期间，有丝分裂在造成神经元损伤方面起着重要作用，最近的研究表明，GLS2 在调节自噬方面起着关键作用。然而，GLS2 究竟如何影响癫痫仍不清楚。目的探讨 GLS2 在癫痫中的表达和分布特点，进而观察癫痫小鼠过表达 GLS2 所引起的行为和电生理变化，并确定 GLS2 是否通过有丝分裂的保护机制调控小鼠模型的癫痫样改变。结果在凯尼酸（KA）诱导的癫痫小鼠模型和谷氨酸琼脂糖诱导的神经元兴奋性损伤 HT22 细胞模型中，GLS2 的表达均出现下调。简而言之，过表达 GLS2 可减轻癫痫活动。随后，我们在KA诱导的癫痫小鼠模型中证实了GLS2与有丝分裂相关蛋白的相互作用。从机制上讲，过表达 GLS2 可抑制癫痫小鼠的有丝分裂，下调 LC3 的表达并减少 ROS 的产生。结论本研究证明癫痫小鼠的 GLS2 表达模式异常。海马神经元的有丝分裂功能受到 GLS2 的影响，过表达 GLS2 可通过改变有丝分裂功能减少癫痫样事件（SLEs）的发生。因此，GLS2 可能控制癫痫发作，我们的发现为抗癫痫治疗提供了一条新途径，并为治疗和预防癫痫提供了新见解。

{"title":"GLS2 reduces the occurrence of epilepsy by affecting mitophagy function in mouse hippocampal neurons","authors":"Yuan Gao, Limin Ma, Jinxian Yuan, Yunyi Huang, Yuenan Ban, Peng Zhang, Dandan Tan, Minxue Liang, Zhipeng Li, Chen Gong, Tao Xu, Xiaolan Yang, Yangmei Chen","doi":"10.1111/cns.70036","DOIUrl":"https://doi.org/10.1111/cns.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Altered mitophagy has been observed in various neurological disorders, such as epilepsy. The role of mitophagy in causing neuronal damage during epileptic episodes is significant, and recent research has indicated that GLS2 plays a crucial role in regulating autophagy. However, exactly how GLS2 affects epilepsy is still unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the expression and distribution characteristics of GLS2 in epilepsy, and then observed the changes in behavior and electrophysiology caused by overexpression of GLS2 in epileptic mice, and determined whether GLS2 regulated seizure-like changes in the mouse model through the protective mechanism of mitophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of GLS2 in a kainic acid (KA)-induced epileptic mouse model and aglutamate-inducedneuronal excitatory damage in HT22 cells model was downregulation. In brief, overexpression of GLS2 can alleviate epileptic activity. Subsequently, we demonstrated that GLS2 interacts with mitophagy-related proteins in a KA-induced epilepsy mouse model. Mechanistically, overexpression of GLS2 inhibited mitophagy in epileptic mice, downregulating the expression of LC3 and reducing ROS production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study proves the GLS2 expression pattern is abnormal in epileptic mice. The function of mitophagy in hippocampal neurons is affected by GLS2, and overexpression of GLS2 can reduce the occurrence of seizure-like events (SLEs) by altering mitophagy function. Thus, GLS2 might control seizures, and our findings provide a fresh avenue for antiepileptic treatment and offer novel insights into treating and preventing epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to “Reduced Risk Tolerance and Cortical Excitability Following COVID-19 Infection” 对 "COVID-19 感染后风险耐受性和皮层兴奋性降低 "的更正。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-11 DOI: 10.1111/cns.70080

Y. Wang, H. Yang, C. Wang, T. F. Yuan, and S. Zhang, “Reduced Risk Tolerance and Cortical Excitability Following COVID-19 Infection,” CNS Neuroscience & Therapeutics 30, no. 8 (2024): e14879.

In the Table 1, n = 31 in both uninfected and infected group was incorrect. This should have read: n = 26 in uninfected group and n = 26 in infected group. Following is the revised table.

We apologize for this error.

Y.Wang, H. Yang, C. Wang, T. F. Yuan, and S. Zhang, "Reduced Risk Tolerance and Cortical Excitability Following COVID-19 Infection," CNS Neuroscience & Therapeutics 30, no. 8 (2024): e14879.在表 1 中，未感染组和感染组的 n = 31 不正确。应为：未感染组 n = 26，感染组 n = 26。以下是修订后的表格。我们对这一错误表示歉意。

引用次数: 0

Microglial priming by IFN-γ involves STAT1-mediated activation of the NLRP3 inflammasome IFN-γ 对小胶质细胞的引诱作用涉及 STAT1 介导的 NLRP3 炎性体的激活。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-11 DOI: 10.1111/cns.70061

Haili He, Xiaomei Zhang, Hui He, Gaojie Xu, Liangyuan Li, Chengyan Yang, Yu-e Liu, Zili You, Jinqiang Zhang

Background

Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)-γ is known to cause microglial priming, but the mechanism is unclear.

Methods

We examined the effects of IFN-γ on gene expression, microglial activation, inflammatory and immune responses and activity of the NLRP3 inflammasome in primary microglia and in the brains of mice.

Results

Our results showed that treating microglial cultures with IFN-γ induced a hedgehog-like morphology and upregulated markers of microglial activation (CD86, CD11b) and pro-inflammatory molecules (IL-1β, IL-6, TNF-α, iNOS), while downregulating markers of microglial homeostasis (CX3CR1, CD200R1), anti-inflammatory molecules (MCR1, Arg-1) and neurotrophic factors (IGF-1, BDNF). IFN-γ also upregulated markers of NLRP3 inflammasome activation (NLRP3, caspase-1, gasdermin D, IL-18). This particular transcriptional profiling makes IFN-γ-primed microglia with exaggerated responses upon lipopolysaccharide (LPS) stimulation. The level of NLRP3, caspase-1, gasdermin D, IL-1β, IL-18, TNF-α and iNOS in microglia cultures treated with both IFN-γ and LPS were highest than with either one alone. Injecting IFN-γ into the lateral ventricle of mice induced similar morphological and functional changes in hippocampal microglia as in primary microglial cultures. The effects of IFN-γ on NLRP3 inflammasome and microglia from cultures or hippocampus were abolished when STAT1 was inhibited using fludarabin. Injecting mice with IFN-γ alone or together with LPS induced anxiety- and depression-like behaviors and impaired hippocampus-dependent spatial memory; these effects were mitigated by fludarabin.

Conclusions

IFN-γ primes microglia by activating STAT1, which upregulates genes that activate the NLRP3 inflammasome. Inhibiting the IFN-γ/STAT1 axis may be a way to treat neurodegenerative diseases and psychiatric disorders that involve microglial priming.

背景：导致各种神经精神疾病的脑部炎症和免疫反应可能始于小胶质细胞 "启动"。已知干扰素（IFN）-γ可导致小胶质细胞 "启动"，但其机制尚不清楚：我们研究了 IFN-γ 对原代小胶质细胞和小鼠大脑中基因表达、小胶质细胞活化、炎症和免疫反应以及 NLRP3 炎性体活性的影响：结果表明：用 IFN-γ 处理小胶质细胞培养物会诱导刺猬样形态，上调小胶质细胞活化标志物（CD86、CD11b）和促炎分子（IL-1β、IL-6、TNF-α、iNOS），同时下调小胶质细胞稳态标志物（CX3CR1、CD200R1）、抗炎分子（MCR1、Arg-1）和神经营养因子（IGF-1、BDNF）。IFN-γ 还能上调 NLRP3 炎症小体激活的标志物（NLRP3、caspase-1、gasdermin D、IL-18）。这种特殊的转录谱分析使 IFN-γ 激发的小胶质细胞在受到脂多糖（LPS）刺激时反应剧烈。在同时接受 IFN-γ 和 LPS 处理的小胶质细胞培养物中，NLRP3、caspase-1、gasdermin D、IL-1β、IL-18、TNF-α 和 iNOS 的水平均高于单独接受其中一种处理的水平。向小鼠侧脑室注射 IFN-γ 可诱导海马小胶质细胞发生与原代小胶质细胞培养物相似的形态和功能变化。当使用氟达拉滨抑制 STAT1 时，IFN-γ 对 NLRP3 炎性体和培养物或海马小胶质细胞的影响就会消失。给小鼠单独注射 IFN-γ 或同时注射 LPS 会诱发焦虑和抑郁样行为，并损害海马依赖性空间记忆；氟达拉滨可减轻这些影响：结论：IFN-γ 通过激活 STAT1 来激发小胶质细胞，而 STAT1 会上调激活 NLRP3 炎性体的基因。抑制 IFN-γ/STAT1 轴可能是治疗涉及小胶质细胞启动的神经退行性疾病和精神疾病的一种方法。

{"title":"Microglial priming by IFN-γ involves STAT1-mediated activation of the NLRP3 inflammasome","authors":"Haili He, Xiaomei Zhang, Hui He, Gaojie Xu, Liangyuan Li, Chengyan Yang, Yu-e Liu, Zili You, Jinqiang Zhang","doi":"10.1111/cns.70061","DOIUrl":"10.1111/cns.70061","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory and immune responses in the brain that contribute to various neuropsychiatric disorders may begin as microglial “priming”. Interferon (IFN)-γ is known to cause microglial priming, but the mechanism is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the effects of IFN-γ on gene expression, microglial activation, inflammatory and immune responses and activity of the NLRP3 inflammasome in primary microglia and in the brains of mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that treating microglial cultures with IFN-γ induced a hedgehog-like morphology and upregulated markers of microglial activation (CD86, CD11b) and pro-inflammatory molecules (IL-1β, IL-6, TNF-α, iNOS), while downregulating markers of microglial homeostasis (CX3CR1, CD200R1), anti-inflammatory molecules (MCR1, Arg-1) and neurotrophic factors (IGF-1, BDNF). IFN-γ also upregulated markers of NLRP3 inflammasome activation (NLRP3, caspase-1, gasdermin D, IL-18). This particular transcriptional profiling makes IFN-γ-primed microglia with exaggerated responses upon lipopolysaccharide (LPS) stimulation. The level of NLRP3, caspase-1, gasdermin D, IL-1β, IL-18, TNF-α and iNOS in microglia cultures treated with both IFN-γ and LPS were highest than with either one alone. Injecting IFN-γ into the lateral ventricle of mice induced similar morphological and functional changes in hippocampal microglia as in primary microglial cultures. The effects of IFN-γ on NLRP3 inflammasome and microglia from cultures or hippocampus were abolished when STAT1 was inhibited using fludarabin. Injecting mice with IFN-γ alone or together with LPS induced anxiety- and depression-like behaviors and impaired hippocampus-dependent spatial memory; these effects were mitigated by fludarabin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IFN-γ primes microglia by activating STAT1, which upregulates genes that activate the NLRP3 inflammasome. Inhibiting the IFN-γ/STAT1 axis may be a way to treat neurodegenerative diseases and psychiatric disorders that involve microglial priming.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neobavaisoflavone Ameliorates Memory Deficits and Brain Damage in Aβ25-35-Induced Mice by Regulating SIRT1 新巴西异黄酮通过调节SIRT1改善Aβ25-35诱导小鼠的记忆缺陷和脑损伤

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-11 DOI: 10.1111/cns.70068

Fengxiao Hao, Mengnan Zeng, Bing Cao, Xiwen Liang, Kaili Ye, Xinmian Jiao, Weisheng Feng, Xiaoke Zheng

Background

Alzheimer's disease (AD) is a common chronic neurodegenerative disease in older people, and there is no specific treatment that can stop or reverse its progression. Neobavaisoflavone (NBIF) is a flavonoid that has been shown to have neuroprotective effects, but its role in AD has not been revealed. The present study investigated the role and mechanism of NBIF on Aβ_25-35-induced brain injury.

Methods

In this experiment, the AD mouse model was established by injection of Aβ_25-35 peptides (200 μM, icv), and Donepezil (Don, 10 mg/kg/days), NBIF-L (15 mg/kg/days), and NBIF-H (30 mg/kg/days) were administered orally for 4 weeks. Learning memory, hippocampal pathological changes, pathological markers, apoptosis, oxidative stress, inflammation, immune cells were measured in mice. Network pharmacology combined with the GEO database led to the identification of SIRT1, a key target for NBIF intervention in AD, and levels of SIRT1, p-STAT3 and FOXO1 were measured. In addition, the antagonistic activity of SIRT1 transfection silencing against NBIF in Aβ_25-35-induced in N9 cells and N2a-APP69 cells was investigated to assess whether the effects caused by NBIF were mediated by SIRT1.

Results

The results showed that NBIF ameliorated learning memory and hippocampal neuronal damage, reduced pathological markers, apoptosis, oxidative stress and neuroinflammation, and modulated immune cells. SIRT1 is a key target for NBIF intervention in AD, and NBIF upregulates SIRT1 and reduces the expression levels of p-STAT3 and FOXO1. Furthermore, silencing SIRT1 effectively reduced the protective effect of NBIF on Aβ_25-35-induced N9 cells and N2a-APP69 cells, which indicated that the protective effect of NBIF on AD is related to SIRT1.

Conclusions

NBIF ameliorated Aβ_25-35-induced brain injury by inhibiting apoptosis, oxidative stress, and neuroinflammation, which may be mediated through SIRT1 signaling. These findings provide a rationale for NBIF in the treatment of AD and help facilitate the development of clinical therapeutic agents for AD.

背景：阿尔茨海默病（AD）是老年人常见的慢性神经退行性疾病，目前尚无特效治疗方法可以阻止或逆转其进展。新巴西异黄酮（Neobavaisoflavone，NBIF）是一种类黄酮，已被证明具有神经保护作用，但其在阿尔茨海默病中的作用尚未被揭示。本研究探讨了NBIF对Aβ25-35诱导的脑损伤的作用和机制：本实验通过注射Aβ25-35肽（200 μM，icv）建立AD小鼠模型，口服多奈哌齐（Don，10 mg/kg/days）、NBIF-L（15 mg/kg/days）和NBIF-H（30 mg/kg/days）4周。对小鼠的学习记忆、海马病理变化、病理标志物、细胞凋亡、氧化应激、炎症、免疫细胞进行了测定。网络药理学与 GEO 数据库相结合，确定了 SIRT1（NBIF 干预 AD 的关键靶点），并测量了 SIRT1、p-STAT3 和 FOXO1 的水平。此外，还研究了SIRT1转染沉默对Aβ25-35诱导的N9细胞和N2a-APP69细胞中NBIF的拮抗活性，以评估NBIF引起的效应是否由SIRT1介导：结果表明，NBIF可改善学习记忆和海马神经元损伤，减少病理标志物、细胞凋亡、氧化应激和神经炎症，并调节免疫细胞。SIRT1是NBIF干预AD的关键靶点，NBIF可上调SIRT1，降低p-STAT3和FOXO1的表达水平。此外，沉默SIRT1可有效降低NBIF对Aβ25-35诱导的N9细胞和N2a-APP69细胞的保护作用，这表明NBIF对AD的保护作用与SIRT1有关：结论：NBIF通过抑制细胞凋亡、氧化应激和神经炎症改善了Aβ25-35诱导的脑损伤，这可能是通过SIRT1信号传导介导的。这些发现为NBIF治疗AD提供了理论依据，有助于促进AD临床治疗药物的开发。

{"title":"Neobavaisoflavone Ameliorates Memory Deficits and Brain Damage in Aβ25-35-Induced Mice by Regulating SIRT1","authors":"Fengxiao Hao, Mengnan Zeng, Bing Cao, Xiwen Liang, Kaili Ye, Xinmian Jiao, Weisheng Feng, Xiaoke Zheng","doi":"10.1111/cns.70068","DOIUrl":"10.1111/cns.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is a common chronic neurodegenerative disease in older people, and there is no specific treatment that can stop or reverse its progression. Neobavaisoflavone (NBIF) is a flavonoid that has been shown to have neuroprotective effects, but its role in AD has not been revealed. The present study investigated the role and mechanism of NBIF on Aβ<sub>25-35</sub>-induced brain injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this experiment, the AD mouse model was established by injection of Aβ<sub>25-35</sub> peptides (200 μM, icv), and Donepezil (Don, 10 mg/kg/days), NBIF-L (15 mg/kg/days), and NBIF-H (30 mg/kg/days) were administered orally for 4 weeks. Learning memory, hippocampal pathological changes, pathological markers, apoptosis, oxidative stress, inflammation, immune cells were measured in mice. Network pharmacology combined with the GEO database led to the identification of SIRT1, a key target for NBIF intervention in AD, and levels of SIRT1, p-STAT3 and FOXO1 were measured. In addition, the antagonistic activity of SIRT1 transfection silencing against NBIF in Aβ<sub>25-35</sub>-induced in N9 cells and N2a-APP69 cells was investigated to assess whether the effects caused by NBIF were mediated by SIRT1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that NBIF ameliorated learning memory and hippocampal neuronal damage, reduced pathological markers, apoptosis, oxidative stress and neuroinflammation, and modulated immune cells. SIRT1 is a key target for NBIF intervention in AD, and NBIF upregulates SIRT1 and reduces the expression levels of p-STAT3 and FOXO1. Furthermore, silencing SIRT1 effectively reduced the protective effect of NBIF on Aβ<sub>25-35</sub>-induced N9 cells and N2a-APP69 cells, which indicated that the protective effect of NBIF on AD is related to SIRT1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NBIF ameliorated Aβ<sub>25-35</sub>-induced brain injury by inhibiting apoptosis, oxidative stress, and neuroinflammation, which may be mediated through SIRT1 signaling. These findings provide a rationale for NBIF in the treatment of AD and help facilitate the development of clinical therapeutic agents for AD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity SOXC 通过调节 RhoA 和 RAC1/CDC42 通路的活性，增强 NGN2 介导的胶质母细胞瘤细胞向神经元样细胞的重编程。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-10 DOI: 10.1111/cns.70075

Jianjing Yang, Xiaohong Zhu, Fan Wang, Zhen Chen, Ying Zhang, Jiawei Chen, Haoqi Ni, Chun-Li Zhang, Qichuan Zhuge

Background

Glioblastoma represents the most frequently diagnosed malignant neoplasm within the central nervous system. Human glioblastoma cells can be phenotypically reprogrammed into neuron-like cells through the forced expression of NEUROG2 and SOXC factors. NEUROG2 serves as a pioneer factor, establishing an initial framework for this transformation. However, the specific role of SOXC factors has not been fully elucidated.

Methods

In this study, we used ChIP-seq to determine the potential target gene of NGN2. RNA-seq has been used to evaluate the transcriptional change during NGN2-SOX11-mediated neuron reprogramming. Immunofluorescence was used to determine the neuron reprogramming efficacy and cell proliferation ability. ChIP-qPCR, Co-IP, and Western Blot were performed to investigate the mechanism.

Results

Our findings reveal that SOXC factors, in contrast to their previously identified function as transcriptional activators, act as transcriptional repressors. They achieve this by recruiting TRIM28 to suppress the expression of ECT2, a RhoGEF. This suppression results in the differential regulation of RhoA, RAC1, and CDC42 activities throughout the reprogramming process. We further establish that small molecules targeting RhoA and its effectors can substitute for SOXC factors in facilitating the neuronal reprogramming of glioblastoma cells.

Conclusion

These results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets.

背景：胶质母细胞瘤是中枢神经系统中最常见的恶性肿瘤。通过强制表达 NEUROG2 和 SOXC 因子，人类胶质母细胞瘤细胞可表型重编程为神经元样细胞。NEUROG2 作为先驱因子，为这种转变建立了初始框架。然而，SOXC因子的具体作用尚未完全阐明：在这项研究中，我们使用 ChIP-seq 来确定 NGN2 的潜在靶基因。RNA-seq用于评估NGN2-SOX11介导的神经元重编程过程中的转录变化。免疫荧光用于确定神经元重编程的有效性和细胞增殖能力。为了研究其机制，还进行了 ChIP-qPCR、Co-IP 和 Western Blot：结果：我们的研究结果表明，SOXC因子与之前确定的转录激活因子功能不同，它们起着转录抑制因子的作用。它们通过招募 TRIM28 来抑制 RhoGEF ECT2 的表达。这种抑制导致整个重编程过程中 RhoA、RAC1 和 CDC42 活性的不同调控。我们进一步证实，靶向RhoA及其效应因子的小分子可以替代SOXC因子，促进胶质母细胞瘤细胞的神经元重编程：这些结果强调了 SOXC 因子在转录抑制中的关键作用，并阐明了它们的一个特定下游靶点。

{"title":"SOXC Enhances NGN2-Mediated Reprogramming of Glioblastoma Cells Into Neuron-Like Cells by Modulating RhoA and RAC1/CDC42 Pathway Activity","authors":"Jianjing Yang, Xiaohong Zhu, Fan Wang, Zhen Chen, Ying Zhang, Jiawei Chen, Haoqi Ni, Chun-Li Zhang, Qichuan Zhuge","doi":"10.1111/cns.70075","DOIUrl":"10.1111/cns.70075","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma represents the most frequently diagnosed malignant neoplasm within the central nervous system. Human glioblastoma cells can be phenotypically reprogrammed into neuron-like cells through the forced expression of NEUROG2 and SOXC factors. NEUROG2 serves as a pioneer factor, establishing an initial framework for this transformation. However, the specific role of SOXC factors has not been fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we used ChIP-seq to determine the potential target gene of NGN2. RNA-seq has been used to evaluate the transcriptional change during NGN2-SOX11-mediated neuron reprogramming. Immunofluorescence was used to determine the neuron reprogramming efficacy and cell proliferation ability. ChIP-qPCR, Co-IP, and Western Blot were performed to investigate the mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings reveal that SOXC factors, in contrast to their previously identified function as transcriptional activators, act as transcriptional repressors. They achieve this by recruiting TRIM28 to suppress the expression of ECT2, a RhoGEF. This suppression results in the differential regulation of RhoA, RAC1, and CDC42 activities throughout the reprogramming process. We further establish that small molecules targeting RhoA and its effectors can substitute for SOXC factors in facilitating the neuronal reprogramming of glioblastoma cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-On Trial Treatment for Acute Bipolar Depression Patients With Suicidal Ideation 经颅直流电刺激作为对有自杀意念的急性双相抑郁症患者的附加试验治疗的有效性和安全性。

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-09 DOI: 10.1111/cns.70077

Dandan Wang, Xiaonan Guo, Qi Huang, Zhong Wang, Jingkai Chen, Shaohua Hu

Aims

Bipolar depression poses an overwhelming suicide risk. We aimed to examine the efficacy and safety of transcranial direct current stimulation (tDCS) combined with quetiapine in bipolar patients as a suicidal intervention.

Methods

In a single-center, double-blind, treatment-naive bipolar depression patients with suicidal ideation were randomly assigned to quetiapine in combination with either active (n = 16) or sham (n = 15) tDCS over the left dorsolateral prefrontal cortex for three consecutive weeks. The 30-min, 2-mA tDCS was conducted twice a day on the weekday of the first week and then once a day on the weekdays of the two following weeks. Primary efficacy outcome measure was the change in the Beck Scale for Suicidal Ideation (BSSI). Secondary outcomes included changes on the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Outcome was evaluated on Day 3 and weekend. Safety outcome was based on the reported adverse reactions.

Results

Active tDCS was superior to sham tDCS on the BSSI at Day 3 and tended to sustain every weekend during the treatment process, compared to baseline. However, no difference between active and sham in HDRS-17 and MADRS was found. Response and remission rate also supported the antisuicide effect of tDCS, with higher response and remission rate in BSSI, but no antidepressant effect, compared to sham, over time. Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort.

Conclusion

The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.

目的：双相抑郁症具有极大的自杀风险。我们旨在研究经颅直流电刺激（tDCS）联合喹硫平对双相抑郁症患者进行自杀干预的有效性和安全性：在一项单中心双盲研究中，有自杀意念的双相抑郁症患者被随机分配接受喹硫平联合左侧背外侧前额叶皮层活性（n = 16）或假性（n = 15）tDCS治疗，连续治疗三周。第一周的工作日每天进行两次，每次 30 分钟，每次 2 毫安，随后两周的工作日每天进行一次。主要疗效指标是贝克自杀意念量表（BSSI）的变化。次要结果包括 17 项汉密尔顿抑郁量表（HDRS-17）和蒙哥马利-阿斯伯格抑郁量表（MADRS）的变化。结果在第 3 天和周末进行评估。安全性结果基于报告的不良反应：结果：与基线相比，在第 3 天的 BSSI 上，活性 tDCS 优于假性 tDCS，并且在治疗过程中的每个周末，活性 tDCS 的疗效都趋于持续。然而，在 HDRS-17 和 MADRS 方面，活性和假性没有差异。反应和缓解率也支持 tDCS 的抗自杀效果，随着时间的推移，BSSI 的反应和缓解率更高，但与假体相比，没有抗抑郁效果。在安全性方面，主动tDCS的耐受性良好，所有不良反应都很轻微，仅限于短暂的头皮不适：tDCS对有自杀意念的急性双相抑郁症患者的抗自杀治疗有效，且副作用极小。

{"title":"Efficacy and Safety of Transcranial Direct Current Stimulation as an Add-On Trial Treatment for Acute Bipolar Depression Patients With Suicidal Ideation","authors":"Dandan Wang, Xiaonan Guo, Qi Huang, Zhong Wang, Jingkai Chen, Shaohua Hu","doi":"10.1111/cns.70077","DOIUrl":"10.1111/cns.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Bipolar depression poses an overwhelming suicide risk. We aimed to examine the efficacy and safety of transcranial direct current stimulation (tDCS) combined with quetiapine in bipolar patients as a suicidal intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a single-center, double-blind, treatment-naive bipolar depression patients with suicidal ideation were randomly assigned to quetiapine in combination with either active (<i>n</i> = 16) or sham (<i>n</i> = 15) tDCS over the left dorsolateral prefrontal cortex for three consecutive weeks. The 30-min, 2-mA tDCS was conducted twice a day on the weekday of the first week and then once a day on the weekdays of the two following weeks. Primary efficacy outcome measure was the change in the Beck Scale for Suicidal Ideation (BSSI). Secondary outcomes included changes on the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Outcome was evaluated on Day 3 and weekend. Safety outcome was based on the reported adverse reactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Active tDCS was superior to sham tDCS on the BSSI at Day 3 and tended to sustain every weekend during the treatment process, compared to baseline. However, no difference between active and sham in HDRS-17 and MADRS was found. Response and remission rate also supported the antisuicide effect of tDCS, with higher response and remission rate in BSSI, but no antidepressant effect, compared to sham, over time. Regarding safety, active tDCS was well tolerated and all the adverse reactions reported were mild and limited to transient scalp discomfort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The tDCS was effective as an antisuicide treatment for acute bipolar depression patients with suicidal ideation, with minimal side effects reported.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultra-early stage lower-grade gliomas: How can we define and differentiate these easily misdiagnosed gliomas through intraoperative molecular diagnosis 超早期低级别胶质瘤：如何通过术中分子诊断界定和区分这些容易误诊的胶质瘤？

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-09 DOI: 10.1111/cns.70044

Zhe Han, Qingtong Wang, Jia Li, Huizhong Chi, Caizhi Ma, Deze Jia, Mei Qi, Xueen Li, Kailiang Zhang, Zichao Feng, Hao Xue, Gang Li

<div> <section> <h3> Background</h3> <p>Some lower-grade gliomas (LGG) are difficult to distinguish morphologically from glial cell proliferation or inflammatory changes during surgery, leading to a high risk of incorrect diagnosis. It is crucial to differentiate between the two for making surgical decisions. We define these critical cases as “ultra early stage lower-grade gliomas (UES-LGG)”.</p> </section> <section> <h3> Methods</h3> <p>We analyzed 11 out of 13 cases diagnosed with “gliosis” or “inflammatory changes” during surgery who tested positive for isocitrate dehydrogenase (IDH). Additionally, we conducted qRT-PCR detection on 35 samples diagnosed with LGG during surgery and analyzed their DNA content within an effective circulating threshold range to infer the critical value between UES-LGG and LGG. We conducted experiments using five standardized samples to infer the limited range of accurate detection of UES-LGG during surgery.</p> </section> <section> <h3> Results</h3> <p>In the comparative analysis of 11 samples and 35 samples, it was found that while there was no significant difference in the average DNA detection concentration between the two groups (159.36 ± 83.3 ng/μL and 146.83 ± 122.43 ng/μL), there was a notable statistical variance in the detection threshold for positive mutations (31.78 ± 1.14 and 26.14 ± 2.69, respectively). This suggests that the IDH mutation rate may serve as an indicator for differentiation between the two groups. Subsequently, DNA was extracted from standardized IDH mutant samples and subjected to gradient dilution for detection purposes. The results indicated a consistent increase in detection threshold as detection concentration decreased. When the detection concentration fell below <0.1 ng/μL, it became impossible to carry out effective threshold range detections. To further identify the precise detection interval, we conducted gradient division once again and sought to simulate the functional relationship between DNA copy number and cycle threshold within this interval. The research revealed that when the minimum detection concentration exceeded 250 copies/μL, a 100% detection rate could be achieved.</p> </section> <section> <h3> Conclusions</h3> <p>This article defines UES-LGG as a tumor type easily misdiagnosed in clinical practice due to its extremely low positivity rate during surgery. The popularization of qRT-PCR based intraoperative molecular diagnosis greatly reduces errors caused by manual detection and improves disease detection rates during surgery. It provides a theoretical basis for mo

背景：一些低级别胶质瘤（LGG）在手术中很难从形态学上与胶质细胞增生或炎症改变区分开来，导致误诊的风险很高。区分两者对于手术决策至关重要。我们将这些危重病例定义为 "超早期低级别胶质瘤（UES-LGG）"：我们分析了 13 例在手术中被诊断为 "胶质病变 "或 "炎症改变 "的病例中的 11 例，这些病例的异柠檬酸脱氢酶（IDH）检测结果呈阳性。此外，我们还对 35 例手术中被诊断为 LGG 的样本进行了 qRT-PCR 检测，并在有效循环阈值范围内分析了其 DNA 含量，以推断 UES-LGG 与 LGG 之间的临界值。我们使用 5 份标准化样本进行了实验，以推断手术中 UES-LGG 准确检测的有限范围：在对 11 个样本和 35 个样本的对比分析中发现，虽然两组样本的平均 DNA 检测浓度没有显著差异（159.36 ± 83.3 ng/μL 和 146.83 ± 122.43 ng/μL），但阳性突变的检测临界值却存在明显的统计学差异（分别为 31.78 ± 1.14 和 26.14 ± 2.69）。这表明，IDH 突变率可作为区分两组的指标。随后，从标准化的 IDH 突变样本中提取 DNA 并进行梯度稀释检测。结果表明，随着检测浓度的降低，检测阈值持续上升。当检测浓度低于结论值时，检测阈值就会降低：本文将 UES-LGG 定义为一种在临床实践中容易被误诊的肿瘤类型，因为它在手术中的阳性率极低。基于 qRT-PCR 的术中分子诊断技术的推广，大大减少了人工检测造成的误差，提高了手术中的疾病检出率。它为外科医生制定更精确的手术方案提供了理论依据。

{"title":"Ultra-early stage lower-grade gliomas: How can we define and differentiate these easily misdiagnosed gliomas through intraoperative molecular diagnosis","authors":"Zhe Han, Qingtong Wang, Jia Li, Huizhong Chi, Caizhi Ma, Deze Jia, Mei Qi, Xueen Li, Kailiang Zhang, Zichao Feng, Hao Xue, Gang Li","doi":"10.1111/cns.70044","DOIUrl":"10.1111/cns.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Some lower-grade gliomas (LGG) are difficult to distinguish morphologically from glial cell proliferation or inflammatory changes during surgery, leading to a high risk of incorrect diagnosis. It is crucial to differentiate between the two for making surgical decisions. We define these critical cases as “ultra early stage lower-grade gliomas (UES-LGG)”.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 11 out of 13 cases diagnosed with “gliosis” or “inflammatory changes” during surgery who tested positive for isocitrate dehydrogenase (IDH). Additionally, we conducted qRT-PCR detection on 35 samples diagnosed with LGG during surgery and analyzed their DNA content within an effective circulating threshold range to infer the critical value between UES-LGG and LGG. We conducted experiments using five standardized samples to infer the limited range of accurate detection of UES-LGG during surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the comparative analysis of 11 samples and 35 samples, it was found that while there was no significant difference in the average DNA detection concentration between the two groups (159.36 ± 83.3 ng/μL and 146.83 ± 122.43 ng/μL), there was a notable statistical variance in the detection threshold for positive mutations (31.78 ± 1.14 and 26.14 ± 2.69, respectively). This suggests that the IDH mutation rate may serve as an indicator for differentiation between the two groups. Subsequently, DNA was extracted from standardized IDH mutant samples and subjected to gradient dilution for detection purposes. The results indicated a consistent increase in detection threshold as detection concentration decreased. When the detection concentration fell below <0.1 ng/μL, it became impossible to carry out effective threshold range detections. To further identify the precise detection interval, we conducted gradient division once again and sought to simulate the functional relationship between DNA copy number and cycle threshold within this interval. The research revealed that when the minimum detection concentration exceeded 250 copies/μL, a 100% detection rate could be achieved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This article defines UES-LGG as a tumor type easily misdiagnosed in clinical practice due to its extremely low positivity rate during surgery. The popularization of qRT-PCR based intraoperative molecular diagnosis greatly reduces errors caused by manual detection and improves disease detection rates during surgery. It provides a theoretical basis for mo","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parietal memory network and memory encoding versus retrieval impairments in PD-MCI patients: A hippocampal volume and cortical thickness study 顶叶记忆网络和PD-MCI患者的记忆编码与检索损伤：海马体积和皮质厚度研究

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics

Pub Date : 2024-10-08 DOI: 10.1111/cns.70062

Serhat Sahin, Halil Aziz Velioglu, Burak Yulug, Zubeyir Bayraktaroglu, Suleyman Yildirim, Lutfu Hanoglu

Objective

The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF).

Methods

The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (N = 18) and EF (N = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation.

Results

Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p⟨0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p⟨0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (p > 0.05).

Conclusion

Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment.

目的：帕金森病轻度认知障碍（PD-MCI）患者记忆障碍背后的病理生理学尚不清楚。本研究旨在探讨帕金森病轻度认知障碍（PD-MCI）患者的海马和皮质萎缩模式，这些患者存在不同类型的记忆障碍，分为检索失败（RF）和编码失败（EF）：研究对象包括16名健康对照组（HC）和34名PD-MCI患者，根据他们的言语记忆过程测试（VMPT）得分（包括自发回忆、识别和对线索的敏感性指数（ISC））分为RF组（18人）和EF组（16人）。使用FreeSurfer软件进行自动分割，测量海马亚区和皮层厚度：与 HC 组相比，EF 组的左侧枕叶外侧区、右侧额叶中部尾端区、颞叶上部区和颞叶下部区出现明显萎缩（p⟨0.05）。射频组的左侧枕叶外侧区、颞叶中部区、前中央区以及右侧眶旁区和额叶上部区都出现了明显的萎缩（p⟨0.05）。海马亚区分析显示，HC-EF组和RF-EF组之间存在明显的体积差异，EF组的CA1、CA3和CA4亚区显著减少，但HC组和RF组之间没有差异（P>0.05）：结论：PD-MCI患者的灰质萎缩模式在编码记忆和检索记忆障碍方面存在差异。EF组的海马，尤其是CA亚区的海马明显萎缩，突显了其在疾病进展和记忆衰退中的潜在作用。此外，外侧枕叶皮层的萎缩在 RF 组和 EF 组中趋于一致，这表明顶叶记忆网络（PMN）参与了与 PD 相关的记忆损伤。

{"title":"Parietal memory network and memory encoding versus retrieval impairments in PD-MCI patients: A hippocampal volume and cortical thickness study","authors":"Serhat Sahin, Halil Aziz Velioglu, Burak Yulug, Zubeyir Bayraktaroglu, Suleyman Yildirim, Lutfu Hanoglu","doi":"10.1111/cns.70062","DOIUrl":"10.1111/cns.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (<i>N</i> = 18) and EF (<i>N</i> = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p⟨0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p⟨0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (<i>p</i> > 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"30 10","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0