首页 > 最新文献

Journal of chemical neuroanatomy最新文献

英文 中文
Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain 半帕金森大鼠大脑中代谢型谷氨酸 2/3 型受体的自动放射标记
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-23 DOI: 10.1016/j.jchemneu.2024.102422
Esther Kim , Imane Frouni , Judy Shaqfah , Dominique Bédard , Philippe Huot

L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu2/3) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu2/3 activation, we performed autoradiographic binding with [3H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [3H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, P<0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (49 % vs sham-lesioned rats, P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, P<0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05), GP (34 % vs sham-lesioned rats, P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both P<0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [3H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all P<0.05). These results suggest that alterations in mGlu2/3 receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.

L-3,4-二羟基苯丙氨酸(L-DOPA)是治疗帕金森病(PD)运动症状的首选药物,但其长期使用受到运动障碍等并发症的阻碍。临床前研究发现,激活代谢型谷氨酸 2 型和 3 型(mGlu2/3)受体可减轻 L-DOPA 引起的运动障碍。为了深入了解激活 mGlu2/3 受体抗运动障碍的机理,我们在经 L-DOPA 治疗的 6-羟基多巴胺(6-OHDA)缺失大鼠出现轻度或重度运动障碍的脑切片中,以及未经 L-DOPA 治疗的 6-OHDA 缺失动物和假缺失动物的脑切片中,用[3H]-LY-341,495 进行了自显影结合。在同侧大脑半球,轻度运动障碍的 6-OHDA 失神经节大鼠显示,在内侧脑核(EPN,30% vs 假失神经节大鼠,P<0.05)、苍白球(GP,28% vs 假失神经节大鼠,P<0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001)和初级运动皮层(49 % vs 假缺损大鼠,P<0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, P<0.001)。严重运动障碍的 6-OHDA 失神经节大鼠表现出初级运动皮层结合力增加(43% vs 轻度运动障碍的 6-OHDA 失神经节大鼠,P<0.05)。在对侧半球,轻度运动障碍的 6-OHDA 病变大鼠在 EPN(30 % vs 假缺损大鼠;24 % vs L-DOPA 未处理的 6-OHDA 病变大鼠,均为 P<0.05)、GP(34 % vs L-DOPA 未处理的 6-OHDA 病变大鼠,均为 P<0.0505)、GP(34 % vs 假缺失大鼠,P<0.05;23 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠,P<0.001)和初级运动皮层(50 % vs 假缺失大鼠;44 % vs L-DOPA-untreated 6-OHDA-lesioned 大鼠,均为 P<0.05)。严重运动障碍的 6-OHDA 病变大鼠 GP 结合力下降(30% vs 假缺失大鼠;19% vs L-DOPA 未治疗的 6-OHDA 病变大鼠,均为 P<0.05)。6-OHDA缺失动物的异常不自主运动评分与同侧纹状体、同侧EPN、同侧初级运动皮层和对侧初级运动皮层中的[3H]-LY-341,495结合呈正相关(均为P<0.05)。这些结果表明,mGlu2/3 受体水平的改变可能是缓解运动障碍的内源性代偿机制的一部分。
{"title":"Autoradiographic labelling of metabotropic glutamate type 2/3 receptors in the hemi-parkinsonian rat brain","authors":"Esther Kim ,&nbsp;Imane Frouni ,&nbsp;Judy Shaqfah ,&nbsp;Dominique Bédard ,&nbsp;Philippe Huot","doi":"10.1016/j.jchemneu.2024.102422","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102422","url":null,"abstract":"<div><p>L-3,4-dihydroxyphenylalanine (L-DOPA) is the treatment of choice for Parkinson’s disease (PD) motor symptoms, but its chronic use is hindered by complications such as dyskinesia. Pre-clinical studies discovered that activation of metabotropic glutamate type 2 and 3 (mGlu<sub>2/3</sub>) receptors alleviates L-DOPA-induced dyskinesia. To gain mechanistic insight into the anti-dyskinetic activity of mGlu<sub>2/3</sub> activation, we performed autoradiographic binding with [<sup>3</sup>H]-LY-341,495 in brain sections from L-DOPA-treated 6-hydroxydopamine (6-OHDA)-lesioned rats that developed mild or severe dyskinesia, as well as L-DOPA-untreated 6-OHDA-lesioned and sham-lesioned animals. In the ipsilateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats showed a decrease in [<sup>3</sup>H]-LY-341,495 binding in the entopeduncular nucleus (EPN, 30 % vs sham-lesioned rats, <em>P</em>&lt;0.05), globus pallidus (GP, 28 % vs sham-lesioned rats, <em>P</em>&lt;0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em>&lt;0.001), and primary motor cortex (49 % vs sham-lesioned rats, <em>P</em>&lt;0.05; 45 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em>&lt;0.001). Severely dyskinetic 6-OHDA-lesioned rats exhibited an increase in binding in the primary motor cortex (43 % vs mildly dyskinetic 6-OHDA-lesioned rats, <em>P</em>&lt;0.05). In the contralateral hemisphere, mildly dyskinetic 6-OHDA-lesioned rats harboured a decrease in binding in the EPN (30 % vs sham-lesioned rats; 24 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em>&lt;0.05), GP (34 % vs sham-lesioned rats, <em>P</em>&lt;0.05; 23 % vs L-DOPA-untreated 6-OHDA-lesioned rats, <em>P</em>&lt;0.001), and primary motor cortex (50 % vs sham-lesioned rats; 44 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em>&lt;0.05). Severely dyskinetic 6-OHDA-lesioned rats presented a decrease in binding in the GP (30 % vs sham-lesioned rats; 19 % vs L-DOPA-untreated 6-OHDA-lesioned rats, both <em>P</em>&lt;0.05). Abnormal involuntary movements scores of 6-OHDA-lesioned animals were positively correlated with [<sup>3</sup>H]-LY-341,495 binding in the ipsilateral striatum, ipsilateral EPN, ipsilateral primary motor cortex and contralateral primary motor cortex (all <em>P</em>&lt;0.05). These results suggest that alterations in mGlu<sub>2/3</sub> receptor levels may be part of an endogenous compensatory mechanism to alleviate dyskinesia.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061824000358/pdfft?md5=ec2ef69433d73816b2c7b2d6f385eb7d&pid=1-s2.0-S0891061824000358-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Synergistic action of vitamin D3 and A on motor activity regulation in mice model of extrapyramidal syndrome: Correlational insights into astrocyte regulation, cytokine modulation, and dopaminergic activity 维生素 D3 和维生素 A 对锥体外系综合征小鼠模型运动活动调节的协同作用:关于星形胶质细胞调节、细胞因子调节和多巴胺能活动的相关见解
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-20 DOI: 10.1016/j.jchemneu.2024.102421
Mujittapha U. Sirajo , Yahya K. Maigari , Abdulrashid Sunusi , Adam N. Jibril , Isa Usman Lawal , Badamasi M. Ibrahim

Background

Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear.

Methods

Twenty-four adult mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize reactive astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections.

Results

The EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D&A resulted in significant reductions in IL-6 levels. Only the Vitamin D&A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D&A groups. IL-4 was notably increased in the Vitamin D&A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, and vitamin D&A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other groups.

Conclusions

EPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to suppres pro-inflammatory cytokines and repress anti-inflammatory cytokines associated with astrocyte activation.

背景锥体外系综合征(EPS)是抗精神病药物对神经系统的副作用,以运动障碍为特征。方法将 24 只成年小鼠分为四组:阳性对照组和阴性对照组,一组接受多巴胺拮抗剂治疗,另一组同时接受多巴胺拮抗剂和维生素 D 和 A 治疗。制备皮质基底环的切片,特别是运动皮层(M1)和基底核(CPu),用于免疫组织化学(IHC),并用胶质纤维酸性蛋白(GFAP)染色以观察反应性星形胶质细胞。结果 EPS组M1和CPu中的TNF-α和IL-6水平显著升高。使用多巴胺激动剂和维生素 D&A 治疗后,IL-6 水平显著降低。只有维生素D&A组的TNF-α水平明显下降。EPS组的IL-4和IL-13显著下降,多巴胺激动剂组和维生素D&A组的IL-13显著升高。IL-4 在维生素 D&A 组明显升高。EPS 组的多巴胺浓度明显下降,而接受多巴胺激动剂和维生素 D&A 治疗的各组情况有所改善。结论EPS与星形胶质细胞的活化、促炎细胞因子的激增、抗炎细胞因子的减少以及皮质基底环路中的多巴胺有关。服用维生素 D3 和维生素 A 可抑制促炎细胞因子,抑制与星形胶质细胞活化相关的抗炎细胞因子。
{"title":"Synergistic action of vitamin D3 and A on motor activity regulation in mice model of extrapyramidal syndrome: Correlational insights into astrocyte regulation, cytokine modulation, and dopaminergic activity","authors":"Mujittapha U. Sirajo ,&nbsp;Yahya K. Maigari ,&nbsp;Abdulrashid Sunusi ,&nbsp;Adam N. Jibril ,&nbsp;Isa Usman Lawal ,&nbsp;Badamasi M. Ibrahim","doi":"10.1016/j.jchemneu.2024.102421","DOIUrl":"10.1016/j.jchemneu.2024.102421","url":null,"abstract":"<div><h3>Background</h3><p>Extrapyramidal syndromes (EPS) represent neurological side effects of antipsychotic medications, characterized by motor disturbances. While previous studies have indicated the neuroprotective effects of vitamin D and A against EPS, the underlying mechanisms of this protection remain unclear.</p></div><div><h3>Methods</h3><p>Twenty-four adult mice were categorized into four groups: positive and negative control groups, one receiving a dopamine antagonist, and the other receiving both a dopamine antagonist and vitamins D and A. Sections of the corticobasal loop, specifically the motor cortex (M1) and basal nuclei (CPu), were prepared for Immunohistochemistry (IHC) and stained with Glial Fibrillary Acidic Protein (GFAP) to visualize reactive astrocytes. ELISA assays for TNF-α, IL-6, IL-4, IL-13, and dopamine levels were performed on homogenized brain sections.</p></div><div><h3>Results</h3><p>The EPS group exhibited a significant increase in TNF-α and IL-6 levels in M1 and CPu. Treatment with dopamine agonists and vitamin D&amp;A resulted in significant reductions in IL-6 levels. Only the Vitamin D&amp;A group showed a significant decline in TNF-α. The EPS group recorded significant decreases in IL-4 and IL-13, with IL-13 significantly elevated in the dopamine agonist and Vitamin D&amp;A groups. IL-4 was notably increased in the Vitamin D&amp;A groups. Dopamine concentration significantly declined in the EPS group, with improvements observed in the groups treated with dopamine agonists, and vitamin D&amp;A. Reactive astrocytes were significantly expressed in the M1 and CPu of the EPS group but poorly expressed in other groups.</p></div><div><h3>Conclusions</h3><p>EPS is linked to astrocyte activation, an upsurge in pro-inflammatory cytokines, a decline in anti-inflammatory cytokines, and dopamine in the corticobasal loop. Administration of vitamin D3 and A was found to suppres pro-inflammatory cytokines and repress anti-inflammatory cytokines associated with astrocyte activation.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140780664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The detection methods currently available for protein aggregation in neurological diseases 目前可用于检测神经系统疾病中蛋白质聚集的方法
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-16 DOI: 10.1016/j.jchemneu.2024.102420
Jing-Yi Li , Cheng-Mei Zhou , Rui-Lin Jin , Jia-Hui Song , Ke-Chao Yang , Shu-Lei Li , Bai-Hong Tan , Yan-Chao Li

Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation in situ under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.

蛋白质聚集是各种神经退行性疾病的一个病理特征,被认为在神经系统疾病的发生和发展中起着至关重要的作用。这一病理现象已引起研究人员越来越多的关注,但其潜在机制尚未完全阐明。研究人员越来越希望找到能有效检测蛋白质聚集或保持蛋白质稳定性以防止聚集形成的化学物质或方法。迄今为止,已有多种检测蛋白质聚集的方法,包括荧光相关光谱法、电子显微镜法和分子检测法。遗憾的是,目前仍缺乏在显微镜下原位观察蛋白质聚集的方法。本文回顾了蛋白质聚集的两个主要方面:蛋白质聚集的机制和检测方法。目的是为开发研究这一病理现象的新方法提供线索。
{"title":"The detection methods currently available for protein aggregation in neurological diseases","authors":"Jing-Yi Li ,&nbsp;Cheng-Mei Zhou ,&nbsp;Rui-Lin Jin ,&nbsp;Jia-Hui Song ,&nbsp;Ke-Chao Yang ,&nbsp;Shu-Lei Li ,&nbsp;Bai-Hong Tan ,&nbsp;Yan-Chao Li","doi":"10.1016/j.jchemneu.2024.102420","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102420","url":null,"abstract":"<div><p>Protein aggregation is a pathological feature in various neurodegenerative diseases and is thought to play a crucial role in the onset and progression of neurological disorders. This pathological phenomenon has attracted increasing attention from researchers, but the underlying mechanism has not been fully elucidated yet. Researchers are increasingly interested in identifying chemicals or methods that can effectively detect protein aggregation or maintain protein stability to prevent aggregation formation. To date, several methods are available for detecting protein aggregates, including fluorescence correlation spectroscopy, electron microscopy, and molecular detection methods. Unfortunately, there is still a lack of methods to observe protein aggregation <em>in situ</em> under a microscope. This article reviews the two main aspects of protein aggregation: the mechanisms and detection methods of protein aggregation. The aim is to provide clues for the development of new methods to study this pathological phenomenon.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140604683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chondroitin sulfate proteoglycans mRNA expression and degradation in the zebra finch following traumatic brain injury 斑马雀脑外伤后硫酸软骨素蛋白多糖 mRNA 的表达和降解
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-15 DOI: 10.1016/j.jchemneu.2024.102418
Adam Talwalkar , Gage Haden , Kelli A. Duncan

Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. From minutes to months following damage, injury can result in a complex pathophysiology that can lead to temporary or permanent deficits including an array of neurodegenerative symptoms. These changes can include behavioral dysregulation, memory dysfunctions, and mood changes including depression. The nature and severity of impairments resulting from TBIs vary widely given the range of injury type, location, and extent of brain tissue involved. In response to the injury, the brain induces structural and functional changes to promote repair and minimize injury size. Despite its high prevalence, effective treatment strategies for TBI are limited. PNNs are part of the neuronal extracellular matrix (ECM) that mediate synaptic stabilization in the adult brain and thus neuroplasticity. They are associated mostly with inhibitory GABAergic interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance of the brain. The major structural components of PNNs include multiple chondroitin sulfate proteoglycans (CSPGs) as well as other structural proteins. Here we examine the effects of injury on CSPG expression, specifically around the changes in the side change moieties. To investigate CSPG expression following injury, adult male and female zebra finches received either a bilateral penetrating, or no injury and qPCR analysis and immunohistochemistry for components of the CSPGs were examined at 1- or 7-days post-injury. Next, to determine if CSPGs and thus PNNs should be a target for therapeutic intervention, CSPG side chains were degraded at the time of injury with chondroitinase ABC (ChABC) CSPGs moieties were examined. Additionally, GABA receptor mRNA and aromatase mRNA expression was quantified following CSPG degradation as they have been implicated in neuronal survival and neurogenesis. Our data indicate the CSPG moieties change following injury, potentially allowing for a brief period of synaptic reorganization, and that treatments that target CSPG side chains are successful in further targeting this brief critical period by decreasing GABA mRNA receptor expression, but also decreasing aromatase expression.

创伤性脑损伤(TBI)是导致全球死亡和残疾的主要原因之一。从损伤后数分钟到数月不等,损伤可导致复杂的病理生理学,从而导致暂时性或永久性的功能障碍,包括一系列神经退行性症状。这些变化可能包括行为失调、记忆功能障碍和包括抑郁症在内的情绪变化。由于损伤类型、位置和涉及脑组织的范围不同,创伤性脑损伤导致的损伤的性质和严重程度也大相径庭。为了应对损伤,大脑会诱发结构和功能变化,以促进修复并尽量缩小损伤范围。尽管创伤性脑损伤发病率很高,但有效的治疗策略却很有限。PNNs 是神经元细胞外基质(ECM)的一部分,在成人大脑中介导突触稳定,进而促进神经可塑性。它们主要与抑制性 GABA 能中间神经元相关,被认为负责维持大脑的兴奋/抑制平衡。PNNs的主要结构成分包括多种硫酸软骨素蛋白多糖(CSPGs)以及其他结构蛋白。在此,我们研究了损伤对 CSPG 表达的影响,特别是围绕侧变分子的变化。为了研究损伤后 CSPG 的表达,成年雄性斑马雀和雌性斑马雀分别接受了双侧穿透性损伤或无损伤,并在损伤后 1 天或 7 天对 CSPG 的成分进行了 qPCR 分析和免疫组化检查。接下来,为了确定 CSPGs 以及 PNNs 是否应成为治疗干预的目标,在损伤时用软骨素酶 ABC(ChABC)降解了 CSPGs 侧链,并对 CSPGs 分子进行了检测。此外,还对 CSPG 降解后 GABA 受体 mRNA 和芳香化酶 mRNA 的表达进行了量化,因为它们与神经元存活和神经发生有关。我们的数据表明,CSPG分子在损伤后会发生变化,可能会有一个短暂的突触重组期,针对CSPG侧链的治疗可通过降低GABA mRNA受体的表达,同时也降低芳香化酶的表达,成功地进一步针对这一短暂的关键期进行治疗。
{"title":"Chondroitin sulfate proteoglycans mRNA expression and degradation in the zebra finch following traumatic brain injury","authors":"Adam Talwalkar ,&nbsp;Gage Haden ,&nbsp;Kelli A. Duncan","doi":"10.1016/j.jchemneu.2024.102418","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102418","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. From minutes to months following damage, injury can result in a complex pathophysiology that can lead to temporary or permanent deficits including an array of neurodegenerative symptoms. These changes can include behavioral dysregulation, memory dysfunctions, and mood changes including depression. The nature and severity of impairments resulting from TBIs vary widely given the range of injury type, location, and extent of brain tissue involved. In response to the injury, the brain induces structural and functional changes to promote repair and minimize injury size. Despite its high prevalence, effective treatment strategies for TBI are limited. PNNs are part of the neuronal extracellular matrix (ECM) that mediate synaptic stabilization in the adult brain and thus neuroplasticity. They are associated mostly with inhibitory GABAergic interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance of the brain. The major structural components of PNNs include multiple chondroitin sulfate proteoglycans (CSPGs) as well as other structural proteins. Here we examine the effects of injury on CSPG expression, specifically around the changes in the side change moieties. To investigate CSPG expression following injury, adult male and female zebra finches received either a bilateral penetrating, or no injury and qPCR analysis and immunohistochemistry for components of the CSPGs were examined at 1- or 7-days post-injury. Next, to determine if CSPGs and thus PNNs should be a target for therapeutic intervention, CSPG side chains were degraded at the time of injury with chondroitinase ABC (ChABC) CSPGs moieties were examined. Additionally, GABA receptor mRNA and aromatase mRNA expression was quantified following CSPG degradation as they have been implicated in neuronal survival and neurogenesis. Our data indicate the CSPG moieties change following injury, potentially allowing for a brief period of synaptic reorganization, and that treatments that target CSPG side chains are successful in further targeting this brief critical period by decreasing GABA mRNA receptor expression, but also decreasing aromatase expression.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease 在亨廷顿氏病大鼠模型中,人脐血源性细胞外囊泡通过改善神经肌肉功能和减少胶质细胞病变发挥神经保护作用
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-10 DOI: 10.1016/j.jchemneu.2024.102419
Reza Bahar , Shahram Darabi , Mohsen Norouzian , Susan Roustaei , Shayesteh Torkamani-dordshaikh , Maral Hasanzadeh , Kimia Vakili , Mobina Fathi , Fariba Khodagholi , Neda Kaveh , Shima Jahanbaz , Meysam Hassani Moghaddam , Hojjat-Allah Abbaszadeh , Abbas Aliaghaei

Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.

亨廷顿氏病(Huntington's disease,HD)是一种遗传性疾病,其特征是纹状体中的神经细胞逐渐退化。最近的科学调查显示,细胞外囊泡(EVs)具有缓解炎症和增强运动功能的治疗潜力。本研究的目的是研究在HD大鼠模型中施用从人脐带血(HUCB)中提取的EVs对其运动能力和炎症水平的影响。通过超速离心从人脐带血中制备EVs以确定所获内容物的性质,然后用DLS和透射电子显微镜(TEM)研究了CD标志物81和9的表达、平均大小及其颗粒的形态。然后,为了诱导 HD 模型,向大鼠腹腔注射 3-硝基丙酸(3-NP)神经毒素,经 HUCB-EVs 处理后,对大鼠进行转体、肌电图(EMG)和空场试验。最后,大鼠被处死并取出纹状体后,进行了苏木精和伊红染色(H&E)、体视学、免疫组化、抗氧化测试和免疫印迹。结果表明,HUCB-EVs 的内容物表达 CD9 和 CD81 标记,并呈球形。此外,注射 HUCB-EVs 还能改善运动和神经肌肉功能,减少神经胶质增生,增加抗氧化活性和炎症因子,并能部分防止神经元的减少。研究结果总体表明,HUCB-EVs 具有神经保护作用,并能减轻 3-NP 毒性作用对神经的炎症反应,有利于 HD 的康复。
{"title":"Neuroprotective effect of human cord blood-derived extracellular vesicles by improved neuromuscular function and reduced gliosis in a rat model of Huntington's disease","authors":"Reza Bahar ,&nbsp;Shahram Darabi ,&nbsp;Mohsen Norouzian ,&nbsp;Susan Roustaei ,&nbsp;Shayesteh Torkamani-dordshaikh ,&nbsp;Maral Hasanzadeh ,&nbsp;Kimia Vakili ,&nbsp;Mobina Fathi ,&nbsp;Fariba Khodagholi ,&nbsp;Neda Kaveh ,&nbsp;Shima Jahanbaz ,&nbsp;Meysam Hassani Moghaddam ,&nbsp;Hojjat-Allah Abbaszadeh ,&nbsp;Abbas Aliaghaei","doi":"10.1016/j.jchemneu.2024.102419","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102419","url":null,"abstract":"<div><p>Huntington's disease (HD) is a hereditary condition characterized by the gradual deterioration of nerve cells in the striatum. Recent scientific investigations have revealed the promising potential of Extracellular vesicles (EVs) as a therapy to mitigate inflammation and enhance motor function. This study aimed to examine the impact of administering EVs derived from human umbilical cord blood (HUCB) on the motor abilities and inflammation levels in a rat model of HD. After ultracentrifugation to prepare EVs from HUCB to determine the nature of the obtained contents, the expression of CD markers 81 and 9, the average size and also the morphology of its particles were investigated by DLS and Transmission electron microscopy (TEM). Then, in order to induce the HD model, 3-nitropropionic acid (3-NP) neurotoxin was injected intraperitoneal into the rats, after treatment by HUCB-EVs, rotarod, electromyogram (EMG) and the open field tests were performed on the rats. Finally, after rat sacrifice and the striatum was removed, Hematoxylin and eosin staining (H&amp;E), stereology, immunohistochemistry, antioxidant tests, and western blot were performed. Our results showed that the contents of the HUCB-EVs express the CD9 and CD81 markers and have spherical shapes. In addition, the injection of HUCB-EVs improved motor and neuromuscular function, reduced gliosis, increased antioxidant activity and inflammatory factor, and partially prevented the decrease of neurons. The findings generally show that HUCB-EVs have neuroprotective effects and reduce neuroinflammation from the toxic effects of 3-NP, which can be beneficial for the recovery of HD.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140644647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extrasynaptic distribution of NMDA receptors in cochlear inner hair cell afferent signaling complex 耳蜗内毛细胞传入信号复合体中 NMDA 受体的突触外分布
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-01 DOI: 10.1016/j.jchemneu.2024.102417
Juan Hong , Peidong Dai , Huazheng Liang , Guangbin Sun , Weidong Qi , Yong Bi

Objective

The distribution and role of NMDA receptors is unclear in the afferent signaling complex of the cochlea. The present study aimed to examine the distribution of NMDA receptors in cochlear afferent signaling complex of the adult mouse, and their relationship with ribbon synapses of inner hair cells (IHCs) and GABAergic efferent terminals of the lateral olivocochlear (LOC).

Methods

Immunofluorescence staining in combination with confocal microscopy was used to investigate the distribution of glutamatergic NMDA and AMPA receptors in afferent terminals of SGNs, and their relationship with ribbon synapses of IHCs and GABAergic efferent terminals of LOC.

Results

Terminals with AMPA receptors along with Ribbons of IHC formed afferent synapses in the basal pole of IHCs, and those with NMDA receptors were mainly distributed longitudinally in the IHCs nuclei region. Significant difference was found in the distribution of NMDA and AMPA receptors in IHC afferent signaling complex (P<0.05). Some GABAergic terminals colocalized with NMDA receptors at the IHC nucleus region (P>0.05).

Conclusion

There is significant difference in the distribution of NMDA and AMPA receptors in cochlear afferent signaling complex. NMDA receptors are present in the extra-synaptic region of ribbon synapses of IHCs, and they are related to GABA efferent terminals of the afferent signaling complex.

目的 NMDA受体在耳蜗传入信号复合体中的分布和作用尚不清楚。本研究旨在探讨 NMDA 受体在成年小鼠耳蜗传入信号复合体中的分布及其与内毛细胞(IHC)带状突触和外侧橄榄耳(LOC)GABA 能传出终端的关系。方法采用免疫荧光染色结合共聚焦显微镜研究谷氨酸能NMDA和AMPA受体在SGN传入末端的分布,以及它们与IHC的带状突触和LOC的GABA能传出末端的关系。结果带有AMPA受体的终端与IHC的带状突触在IHC的基极形成传入突触,而带有NMDA受体的终端主要纵向分布在IHC的核区。NMDA和AMPA受体在IHC传入信号复合体中的分布存在显著差异(P<0.05)。结论 NMDA 和 AMPA 受体在耳蜗传入信号复合体中的分布存在显著差异。NMDA受体存在于IHC带状突触的突触外区域,它们与传入信号复合体的GABA传出终端有关。
{"title":"Extrasynaptic distribution of NMDA receptors in cochlear inner hair cell afferent signaling complex","authors":"Juan Hong ,&nbsp;Peidong Dai ,&nbsp;Huazheng Liang ,&nbsp;Guangbin Sun ,&nbsp;Weidong Qi ,&nbsp;Yong Bi","doi":"10.1016/j.jchemneu.2024.102417","DOIUrl":"10.1016/j.jchemneu.2024.102417","url":null,"abstract":"<div><h3>Objective</h3><p>The distribution and role of NMDA receptors is unclear in the afferent signaling complex of the cochlea. The present study aimed to examine the distribution of NMDA receptors in cochlear afferent signaling complex of the adult mouse, and their relationship with ribbon synapses of inner hair cells (IHCs) and GABAergic efferent terminals of the lateral olivocochlear (LOC).</p></div><div><h3>Methods</h3><p>Immunofluorescence staining in combination with confocal microscopy was used to investigate the distribution of glutamatergic NMDA and AMPA receptors in afferent terminals of SGNs, and their relationship with ribbon synapses of IHCs and GABAergic efferent terminals of LOC.</p></div><div><h3>Results</h3><p>Terminals with AMPA receptors along with Ribbons of IHC formed afferent synapses in the basal pole of IHCs, and those with NMDA receptors were mainly distributed longitudinally in the IHCs nuclei region. Significant difference was found in the distribution of NMDA and AMPA receptors in IHC afferent signaling complex (P&lt;0.05). Some GABAergic terminals colocalized with NMDA receptors at the IHC nucleus region (P&gt;0.05).</p></div><div><h3>Conclusion</h3><p>There is significant difference in the distribution of NMDA and AMPA receptors in cochlear afferent signaling complex. NMDA receptors are present in the extra-synaptic region of ribbon synapses of IHCs, and they are related to GABA efferent terminals of the afferent signaling complex.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140356764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Celebrating 37 years of dedication: Reflections on the past and looking toward the future 庆祝 37 年的奉献:回顾过去,展望未来
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-01 DOI: 10.1016/j.jchemneu.2024.102394
Goran Šimić , Gail M. Rodney
{"title":"Celebrating 37 years of dedication: Reflections on the past and looking toward the future","authors":"Goran Šimić ,&nbsp;Gail M. Rodney","doi":"10.1016/j.jchemneu.2024.102394","DOIUrl":"10.1016/j.jchemneu.2024.102394","url":null,"abstract":"","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061824000073/pdfft?md5=c6f295d27ab40f5218d996a246fdcbd4&pid=1-s2.0-S0891061824000073-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139523282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The neurobiological effects of senescence on dopaminergic system: A comprehensive review 衰老对多巴胺能系统的神经生物学影响:综述。
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-04-01 DOI: 10.1016/j.jchemneu.2024.102415
Gabriel S. Rocha , Marco Aurelio M. Freire , Karina M. Paiva , Rodrigo F. Oliveira , Paulo Leonardo A.G. Morais , José Ronaldo Santos , José Rodolfo L.P. Cavalcanti

Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.

随着时间的推移,人体会经历一个自然的、多因素的、持续的过程,这个过程被称为衰老,它在分子、细胞和微观解剖学层面诱发了人体许多系统的变化。大脑作为一个高度复杂的器官,尤其会受到这一过程的影响,有可能损害其众多功能。大脑依靠被称为神经递质的化学信使来正常工作,多巴胺是其中最重要的一种。这种儿茶酚胺在中枢神经系统中发挥着广泛的重要作用,包括运动、学习、认知、动机、情感、奖赏、荷尔蒙释放、记忆巩固、视觉表现、性驱动力、昼夜节律调节和大脑发育。在这篇综合性综述中,我们深入研究了衰老对多巴胺能系统的影响,主要关注 A8 至 A17 多巴胺能核的经典划分。我们深入探讨了它们的解剖和功能,尤其是衰老是如何影响这些核团的。
{"title":"The neurobiological effects of senescence on dopaminergic system: A comprehensive review","authors":"Gabriel S. Rocha ,&nbsp;Marco Aurelio M. Freire ,&nbsp;Karina M. Paiva ,&nbsp;Rodrigo F. Oliveira ,&nbsp;Paulo Leonardo A.G. Morais ,&nbsp;José Ronaldo Santos ,&nbsp;José Rodolfo L.P. Cavalcanti","doi":"10.1016/j.jchemneu.2024.102415","DOIUrl":"10.1016/j.jchemneu.2024.102415","url":null,"abstract":"<div><p>Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Olfactory ensheathing cells as candidate cells for chronic pain treatment 作为慢性疼痛治疗候选细胞的嗅觉鞘细胞
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-03-14 DOI: 10.1016/j.jchemneu.2024.102413
Mei-chen Liu , Qing-fa Guo , Wei-wei Zhang , Hong-liang Luo , Wen-jun Zhang , Hai-jun Hu

Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients’ quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.

慢性疼痛通常伴有组织损伤和痛觉过敏。它容易复发,治愈难度大,严重影响患者的生活质量,是亟待解决的问题。目前的治疗方法主要依赖吗啡类药物,而吗啡类药物并不能从根本上解决神经损伤问题,还可能引起不良反应。因此,近年来科学家们将重点从慢性疼痛治疗转移到细胞移植上。这篇综述通过介绍嗅鞘细胞(OECs)的特点,阐述了慢性疼痛的分类和机制,深入探讨了特殊神经胶质细胞通过吞噬神经碎片、受体配体相互作用、提供营养等抑制神经炎症,最终支持轴突再生和缓解慢性疼痛的作用。本综述通过客观分析相关临床试验和提高疗效的方法以及未来发展前景,总结了 OECs 治疗慢性疼痛的潜力和局限性。
{"title":"Olfactory ensheathing cells as candidate cells for chronic pain treatment","authors":"Mei-chen Liu ,&nbsp;Qing-fa Guo ,&nbsp;Wei-wei Zhang ,&nbsp;Hong-liang Luo ,&nbsp;Wen-jun Zhang ,&nbsp;Hai-jun Hu","doi":"10.1016/j.jchemneu.2024.102413","DOIUrl":"https://doi.org/10.1016/j.jchemneu.2024.102413","url":null,"abstract":"<div><p>Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients’ quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA methylation-altered genes in the rat hippocampal neurogenic niche after continuous exposure to amorphous curcumin 持续暴露于无定形姜黄素后大鼠海马神经源龛中 DNA 甲基化改变的基因
IF 2.8 4区 医学 Q3 Neuroscience Pub Date : 2024-03-13 DOI: 10.1016/j.jchemneu.2024.102414
Qian Tang , Ryota Ojiro , Shunsuke Ozawa , Xinyu Zou , Junta Nakahara , Tomohiro Nakao , Mihoko Koyanagi , Meilan Jin , Toshinori Yoshida , Makoto Shibutani

Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of Gpr150, Mmp23, Rprml, and Pcdh8 as well as the hypomethylation and upregulation of Ppm1j, Fam222a, and Opn3. Immunohistochemically, reprimo-like+ hilar cells and protocadherin-8+ granule cells were decreased and opsin-3+ hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67+ γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by Ctnnb1 and Syp upregulation and Mapk14, Map2k3, and Grip1 downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.

从胚胎阶段就暴露于姜黄素(CUR)无定形配方的大鼠后代具有抗焦虑样行为、增强的恐惧消除学习能力以及海马齿状回(DG)突触可塑性的增强。在本研究中,我们研究了神经源龛中甲基化状态改变的基因与 CUR 暴露后神经功能增强之间的联系。我们在大鼠分娩后第 77 天对暴露于 CUR 的后代进行了 DG 甲基化和 RNA 测序分析。甲基化敏感的高分辨率熔解和实时逆转录 PCR 分别验证了候选基因的甲基化状态和转录水平。在CUR组中,我们证实了Gpr150、Mmp23、Rprml和Pcdh8的高甲基化和下调,以及Ppm1j、Fam222a和Opn3的低甲基化和上调。免疫组化显示,暴露于 CUR 后,reprimo-like+柱状细胞和protocadherin-8+颗粒细胞减少,opsin-3+柱状细胞增加。谷氨酸脱羧酶 67+ γ-氨基丁酸能中间神经元亚群上部分表达了reprimo-like和opsin-3。此外,参与原粘连蛋白-8 介导的 N-粘连蛋白内吞的基因转录水平也随着 CUR 的暴露而改变;与此同时,Ctnnb1 和 Syp 上调,Mapk14、Map2k3 和 Grip1 下调,这表明 CUR 诱导的突触可塑性增强与细胞粘附有关。总之,我们的研究结果表明,在海马神经源龛的不同神经元群中,功能不同的基因的甲基化和表达发生了改变,从而增强了暴露于 CUR 后的突触可塑性。
{"title":"DNA methylation-altered genes in the rat hippocampal neurogenic niche after continuous exposure to amorphous curcumin","authors":"Qian Tang ,&nbsp;Ryota Ojiro ,&nbsp;Shunsuke Ozawa ,&nbsp;Xinyu Zou ,&nbsp;Junta Nakahara ,&nbsp;Tomohiro Nakao ,&nbsp;Mihoko Koyanagi ,&nbsp;Meilan Jin ,&nbsp;Toshinori Yoshida ,&nbsp;Makoto Shibutani","doi":"10.1016/j.jchemneu.2024.102414","DOIUrl":"10.1016/j.jchemneu.2024.102414","url":null,"abstract":"<div><p>Rat offspring who are exposed to an amorphous formula of curcumin (CUR) from the embryonic stage have anti-anxiety-like behaviors, enhanced fear extinction learning, and increased synaptic plasticity in the hippocampal dentate gyrus (DG). In the present study, we investigated the links between genes with altered methylation status in the neurogenic niche and enhanced neural functions after CUR exposure. We conducted methylation and RNA sequencing analyses of the DG of CUR-exposed rat offspring on day 77 after delivery. Methylation status and transcript levels of candidate genes were validated using methylation-sensitive high-resolution melting and real-time reverse-transcription PCR, respectively. In the CUR group, we confirmed the hypermethylation and downregulation of <em>Gpr150</em>, <em>Mmp23</em>, <em>Rprml</em>, and <em>Pcdh8</em> as well as the hypomethylation and upregulation of <em>Ppm1j</em>, <em>Fam222a</em>, and <em>Opn3</em>. Immunohistochemically, reprimo-like<sup>+</sup> hilar cells and protocadherin-8<sup>+</sup> granule cells were decreased and opsin-3<sup>+</sup> hilar cells were increased by CUR exposure. Both reprimo-like and opsin-3 were partially expressed on subpopulations of glutamic acid decarboxylase 67<sup>+</sup> γ-aminobutyric acid-ergic interneurons. Furthermore, the transcript levels of genes involved in protocadherin-8-mediated N-cadherin endocytosis were altered with CUR exposure; this was accompanied by <em>Ctnnb1</em> and <em>Syp</em> upregulation and <em>Mapk14</em>, <em>Map2k3</em>, and <em>Grip1</em> downregulation, suggesting that CUR-induced enhanced synaptic plasticity is associated with cell adhesion. Together, our results indicate that functionally different genes have altered methylation and expression in different neuronal populations of the hippocampal neurogenic niche, thus enhancing synaptic plasticity after CUR exposure.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of chemical neuroanatomy
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1