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New Insights into Contradictory Changes in Brain-Derived Neurotrophic Factor (BDNF) in Rodent Models of Posttraumatic Stress Disorder (PTSD) 创伤后应激障碍(PTSD)啮齿动物模型中脑源性神经营养因子(BDNF)矛盾变化的新发现
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-16 DOI: 10.1007/s11064-024-04242-5
Reza Ghaffarzadegan, Shahin Akhondzadeh, Zahra Nikasa, Shadi Hajizamani, Saba Mehrabanifar, Iman Cheraghi, Salar Vaseghi

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that may develop after experiencing traumatic events. Preclinical studies use various methods to induce PTSD-like models such as fear-conditioning, single-prolonged stress (SPS), restraint stress, and social defeat. Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophin in mood regulation. Evidence shows BDNF changes in different neuropsychiatric disorders particularly PTSD. This review examined BDNF alterations in preclinical rodent models of PTSD where we demonstrated a wide range of paradoxical changes in BDNF. We found that the fear-conditioning model produced the most inconsistent alterations in BDNF, and suggest that conclusions drawn from these changes be approached with caution. We suggest that BDNF maladaptive changes in social defeat and restraint stress models may be related to the duration of stress, while the SPS model appears to have more consistent results. Ultimately, we propose that evaluating BDNF alterations in the process of treating PTSD symptoms may not be a reliable factor.

创伤后应激障碍(PTSD)是一种在经历创伤事件后可能出现的神经精神障碍。临床前研究使用各种方法诱导类似创伤后应激障碍的模型,如恐惧条件反射、单次持续应激(SPS)、束缚应激和社会挫败。脑源性神经营养因子(BDNF)是调节情绪的重要神经营养素。有证据表明,BDNF 在不同的神经精神疾病,尤其是创伤后应激障碍中会发生变化。本综述研究了创伤后应激障碍临床前啮齿动物模型中 BDNF 的变化,我们在这些模型中发现了 BDNF 的多种矛盾变化。我们发现,恐惧条件反射模型产生的 BDNF 变化最不一致,并建议谨慎对待从这些变化中得出的结论。我们认为,社会挫败和束缚应激模型中的 BDNF 适应不良变化可能与应激持续时间有关,而 SPS 模型的结果似乎更为一致。最后,我们建议在治疗创伤后应激障碍症状的过程中评估 BDNF 的变化可能不是一个可靠的因素。
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引用次数: 0
Mirtazapine Improves Locomotor Activity and Attenuates Neuropathic Pain Following Spinal Cord Injury in Rats via Neuroinflammation Modulation 米氮平通过神经炎症调节改善大鼠脊髓损伤后的运动活动并减轻神经性疼痛
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-13 DOI: 10.1007/s11064-024-04240-7
Seyed Hadi Aghili, Mohammad Amin Manavi, Mohammad Panji, Mehri Farhang Ranjbar, Ramin Abrishami, Ahmad Reza Dehpour

Neuroinflammation-related locomotor deficits and neuropathic pain are expected outcomes of spinal cord injury (SCI). The atypical antidepressant mirtazapine has exhibited potential neuroprotective and anti-inflammatory effects. This research aims to investigate the impacts of mirtazapine on post-SCI neuropathic pain and locomotor recovery, with a particular focus on neuroinflammation. The study utilized 30 male Wistar rats divided into five groups: Sham, SCI with vehicle treatment, and SCI administered with mirtazapine (3, 10, and 30 mg/kg/day, ip, for one week). Locomotor activity was assessed using the Basso, Beattie, and Bresnahan (BBB) scale. Mechanical, thermal, and cold allodynia were assessed using von-Frey filaments, tail flick latency, and the acetone test, respectively. ELISA was utilized to measure cytokines, while Western blotting was used to determine TRPV1 channel, 5-HT2A receptor, NLRP3, and iNOS expression. Histopathological analyses were also examined, including hematoxylin and eosin (H&E) and Luxol fast blue (LFB) staining. Mirtazapine (10 and 30 mg/kg/day) significantly improved locomotor recovery according to BBB score. It attenuated mechanical, thermal, and cold allodynia post-SCI. Moreover, it decreased pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-18, while increasing anti-inflammatory cytokine IL-4 and IL-10. Furthermore, it downregulated iNOS, NLRP3, and TRPV1 expression and upregulated the 5-HT2A receptor. H&E and LFB staining further revealed attenuated tissue damage and decreased demyelination. Our findings suggest that mirtazapine can alleviate neuropathic pain and reinforce locomotor recovery post-SCI by modulating neuroinflammatory responses, NLRP3, iNOS, TRPV1 channel, and 5-HT2A receptor expression.

神经炎症相关的运动障碍和神经病理性疼痛是脊髓损伤(SCI)的预期结果。非典型抗抑郁药米氮平具有潜在的神经保护和抗炎作用。本研究旨在调查米氮平对 SCI 后神经病理性疼痛和运动恢复的影响,尤其关注神经炎症。研究使用了 30 只雄性 Wistar 大鼠,分为五组:假体组、接受药物治疗的 SCI 组和接受米氮平(3、10 和 30 毫克/千克/天,ip,一周)治疗的 SCI 组。运动活动采用巴索、比提和布雷斯纳汉(BBB)量表进行评估。机械、热和冷异感分别使用 Von-Frey 细丝、甩尾潜伏期和丙酮试验进行评估。酶联免疫吸附法(ELISA)用于检测细胞因子,而 Western 印迹法(Western blotting)用于检测 TRPV1 通道、5-HT2A 受体、NLRP3 和 iNOS 的表达。此外,还进行了组织病理学分析,包括苏木精和伊红(H&E)以及鲁克索快蓝(LFB)染色。根据 BBB 评分,米氮平(10 和 30 毫克/千克/天)明显改善了运动恢复。它减轻了SCI后的机械、热和冷异敏症。此外,它还减少了促炎细胞因子 TNF-α、IL-1β、IL-6 和 IL-18,同时增加了抗炎细胞因子 IL-4 和 IL-10。此外,它还能下调 iNOS、NLRP3 和 TRPV1 的表达,并上调 5-HT2A 受体。H&E和LFB染色进一步显示组织损伤减轻,脱髓鞘减少。我们的研究结果表明,米氮平可以通过调节神经炎症反应、NLRP3、iNOS、TRPV1 通道和 5-HT2A 受体的表达,缓解神经病理性疼痛并加强 SCI 后的运动恢复。
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引用次数: 0
Neuromedin U Neurons in the Edinger–Westphal Nucleus Respond to Alcohol Without Interfering with the Urocortin 1 Response 艾丁格-西脑核中的神经生长因子 U 对酒精的反应不会干扰尿皮质素 1 的反应
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-12 DOI: 10.1007/s11064-024-04238-1
Mireia Medrano, Wissal Allaoui, Ra’fat Ehab Salim Haddad, Leila Makrini-Maleville, Emmanuel Valjent, Ilse Smolders, Viktória Kormos, Balázs Gaszner, Dimitri De Bundel

The Edinger–Westphal nucleus (EW) is a midbrain nucleus composed of a preganglionic, cholinergic subpopulation and a densely clustered peptidergic subpopulation (EWcp). The EWcp is one of the few brain regions that show consistent induction of FOS following voluntary alcohol intake. Previous results in rodents point to urocortin 1 (UCN1) as one of the peptides most involved in the control of ethanol intake and preference. Notably, the functions described for UCN1, such as reward processing, stress coping or the regulation of feeding behavior are similar to those described for the neuropeptide neuromedin U (NMU). Interestingly, NMU has been recently associated with the modulation of alcohol-related behaviors. However, little is known about the expression and functionality of NMU neurons in alcohol-responsive areas. In this study, we used the recently developed Nmu-Cre knock-in mouse model to examine the expression of NMU in the subaqueductal paramedian zone comprising the EWcp. We delved into the characterization and co-expression of NMU with other markers already described in the EWcp. Moreover, using FOS as a marker of neuronal activity, we tested whether NMU neurons were sensitive to acute alcohol administration. Overall, we provided novel insights on NMU expression and functionality in the EW region. We showed the presence of NMU within a subpopulation of UCN1 neurons in the EWcp and demonstrated that this partial co-expression does not interfere with the responsivity of UCN1-containing cells to alcohol. Moreover, we proposed that the UCN1 content in these neurons may be influenced by sex.

艾丁格-韦斯特脑核(EW)是一个中脑核,由神经节前胆碱能亚群和密集聚集的肽能亚群(EWcp)组成。EWcp 是自愿摄入酒精后持续诱导 FOS 的少数脑区之一。之前在啮齿类动物中的研究结果表明,尿皮质素 1(UCN1)是参与乙醇摄入和偏好控制的最主要多肽之一。值得注意的是,UCN1 的功能(如奖赏处理、压力应对或摄食行为调节)与神经肽神经介素 U(NMU)的功能类似。有趣的是,NMU 最近与酒精相关行为的调节有关。然而,人们对 NMU 神经元在酒精反应区的表达和功能知之甚少。在本研究中,我们利用最近开发的 Nmu-Cre 基因敲入小鼠模型,研究了 NMU 在包括 EWcp 的下导水管旁区的表达情况。我们深入研究了 NMU 与 EWcp 中已描述的其他标记物的特征和共表达。此外,我们使用 FOS 作为神经元活动的标记物,测试了 NMU 神经元是否对急性酒精给药敏感。总之,我们对 NMU 在 EW 区的表达和功能提供了新的见解。我们发现在 EWcp 的 UCN1 神经元亚群中存在 NMU,并证明这种部分共表达不会干扰含 UCN1 细胞对酒精的反应性。此外,我们还提出,这些神经元中的 UCN1 含量可能受性别影响。
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引用次数: 0
Activation of the LKB1/AMPK/HIF-1α Pathway by Metformin to Promote Neovascularisation in Cerebral Ischaemia 二甲双胍激活 LKB1/AMPK/HIF-1α 通路促进脑缺血中的血管新生
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-06 DOI: 10.1007/s11064-024-04235-4
Hongguang Chen, Yuting Yuan, Yue Zhang, Xiufen Liu, Qingjie Chen, Chao Liu, Qing Yao

As a difficult-to-treat neurological condition, cerebral ischemia is currently limited to treatments such as intravenous recombinant tissue plasminogen activator thrombolysis and thrombectomy. Metformin, a potent antidiabetic drug, has been reported to have an independent function in enhancing the prognosis of stroke patients, in addition to its glucose-lowering effects. However, the mechanism of action of metformin in this context remains unclear. In vivo, a rat model of permanent middle cerebral artery occlusion was established, and after administration of a low dose of 10.5 mg/mL metformin, infarct area was measured by TTC staining, and cortical blood flow was determined by laser Doppler imaging. In vitro, the study established human umbilical vein endothelial cells treated with cobalt chloride. Immunofluorescence, immunohistochemistry, and Western blot experiments were performed to observe the expression of angiogenic factors, tight junction proteins, and apoptotic factors. A TUNEL assay was utilized to appraise cell death by apoptosis. A tube formation assay and scratch assay were conducted to determine the endothelial neovascularization status. Animal experiments have revealed that the administration of the AMPK activator metformin significantly reduced the infarct area, promoted the expression of angiogenic factors, and maintained the stability of tight junction proteins in endothelial cells. Moreover, metformin reduces nerve cells apoptosis by affecting the expression of the apoptotic protein cleaved-caspase3 via the HIF-1α pathway. In vitro, the LKB1/AMPK signaling pathway is activated after hypoxic stimulation, attaining its peak within the early stages of hypoxia (1–12 h) and gradually weakening thereafter. The administration of AMPK pharmacological agonists (between 36 and 48 h) can enhance AMPK activity, which can lead to the expression of angiogenic factors, maintain the stability of tight-junction proteins in endothelial cells, and facilitate endothelial cell migration and vascular structure formation. Conversely, the AMPK inhibitors exert the opposite effects. The activation of the LKB1/AMPK/HIF-1α signaling pathway by metformin in cerebral ischemia contributes to angiogenesis, promotes tissue repair in the injured area, and enhances neurologically functional symptoms.

脑缺血是一种难以治疗的神经系统疾病,目前的治疗方法仅限于静脉注射重组组织纤溶酶原激活剂溶栓和血栓切除术。据报道,二甲双胍是一种强效抗糖尿病药物,除降糖作用外,还具有改善脑卒中患者预后的独立功能。然而,二甲双胍在这方面的作用机制仍不清楚。在体内,研究人员建立了大鼠永久性大脑中动脉闭塞模型,在给予低剂量 10.5 毫克/毫升二甲双胍后,通过 TTC 染色测量梗死面积,并通过激光多普勒成像测定皮质血流量。在体外,研究建立了用氯化钴处理的人脐静脉内皮细胞。通过免疫荧光、免疫组织化学和 Western 印迹实验观察血管生成因子、紧密连接蛋白和凋亡因子的表达。利用 TUNEL 试验评估细胞凋亡。通过管形成试验和划痕试验来确定内皮新生血管的状况。动物实验显示,服用 AMPK 激活剂二甲双胍可显著缩小梗死面积,促进血管生成因子的表达,并维持内皮细胞中紧密连接蛋白的稳定性。此外,二甲双胍还能通过HIF-1α途径影响凋亡蛋白裂解-caspase3的表达,从而减少神经细胞凋亡。在体外,LKB1/AMPK 信号通路在缺氧刺激后被激活,在缺氧早期(1-12 小时)达到峰值,之后逐渐减弱。给予 AMPK 药物激动剂(36 至 48 h)可增强 AMPK 活性,从而导致血管生成因子的表达,维持内皮细胞中紧密连接蛋白的稳定性,促进内皮细胞迁移和血管结构的形成。相反,AMPK 抑制剂则会产生相反的作用。二甲双胍对脑缺血患者 LKB1/AMPK/HIF-1α 信号通路的激活有助于血管生成,促进损伤区域的组织修复,并改善神经功能症状。
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引用次数: 0
A Retrospective Tribute to Dr. Harish Pant (1938–2023) and His Seminal Work on Cyclin Dependent Kinase 5 向 Harish Pant 博士(1938-2023 年)及其关于 Cyclin Dependent Kinase 5 的开创性工作致敬。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04234-5
Bradford Hall, Niranjana Amin,  Veeranna, Shin-ichi Hisanaga, Ashok. B. Kulkarni

Dr. Harish Chandra Pant was Chief of the Section on Neuronal Cytoskeletal Protein Regulation within the National Institute of Neurological Disorders and Stroke at the NIH. A main focus of his group was understanding the mechanisms regulating neuronal cytoskeletal phosphorylation. Phosphorylation of neurofilaments can increase filament stability and confer resistance to proteolysis, but aberrant hyperphosphorylation of neurofilaments can be found in the neurofibrillary tangles that are seen with neurodegenerative diseases like Alzheimer disease (AD). Through his work, Harish would inevitably come across cyclin dependent kinase 5 (Cdk5), a key kinase that can phosphorylate neurofilaments at KSPXK motifs. Cdk5 differs from other Cdks in that its activity is mainly in post-mitotic neurons rather than being involved in the cell cycle in dividing cells. With continued interest in Cdk5, Harish and his group were instrumental in identifying important roles for this neuronal kinase in not only neuronal cytoskeleton phosphorylation but also in neuronal development, synaptogenesis, and neuronal survival. Here, we review the accomplishments of Harish in characterizing the functions of Cdk5 and its involvement in neuronal health and disease.

哈里什-钱德拉-潘特博士是美国国立卫生研究院国家神经疾病和中风研究所神经细胞骨架蛋白调控科科长。他的研究小组主要致力于了解神经元细胞骨架磷酸化的调控机制。神经丝的磷酸化可以增加神经丝的稳定性并赋予其抗蛋白水解的能力,但神经丝的异常过度磷酸化可在神经纤维缠结中发现,而神经纤维缠结是阿尔茨海默病(AD)等神经退行性疾病的常见症状。通过工作,哈里什不可避免地接触到了细胞周期蛋白依赖性激酶5(Cdk5),这是一种能在KSPXK基序上磷酸化神经丝的关键激酶。Cdk5 与其他 Cdks 的不同之处在于,它的活性主要存在于有丝分裂后的神经元中,而不是参与分裂细胞的细胞周期。随着人们对 Cdk5 的持续关注,Harish 和他的研究小组在确定这种神经激酶在神经元细胞骨架磷酸化以及神经元发育、突触发生和神经元存活中的重要作用方面发挥了重要作用。在此,我们回顾了哈里什在鉴定 Cdk5 功能及其参与神经元健康和疾病方面取得的成就。
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引用次数: 0
Correction to: Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines 更正:组蛋白去乙酰化酶抑制剂 RGFP109 通过阻断 NF-κB 依赖性转录克服了胶质母细胞瘤细胞株对替莫唑胺的耐药性。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04237-2
Zong-yang Li, Qing-zhong Li, Lei Chen, Bao-dong Chen, Bo Wang, Xie-jun Zhang, Wei-ping Li, Neurochem Res
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引用次数: 0
Brief Pup Separation in Lactation Confers Stress Resistance with Increased Prolactin and Adult Hippocampal Neurogenesis in Postpartum C57BL/6J Dams 产后 C57BL/6J 母鼠在哺乳期短暂的幼崽分离会增加催乳素和成年海马神经发生,从而产生抗应激能力。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04231-8
Lin Zhou, Zuotian Wu, Yixin li, Shanshan Lin, Ling Xiao, Huiling Wang, Gaohua Wang

Prolactin (PRL) assumes a pivotal role during the postpartum phase, particularly within the hippocampus—a region densely populated with receptors for stress hormones, where stress significantly inhibits adult hippocampal neurogenesis (AHN). The reduction in neurogenesis is implicated in the pathogenesis of anxiety and depression. Mothers are at an increased risk of developing depression when exposed to chronic stress. Therefore, it is imperative to investigate the potential role of PRL in depression-like behaviors stemming from prolonged postpartum stress, and to explore any underlying mechanisms. Despite pup separation (PS) being a natural postpartum care practice, the impact of various PS methods on lactating dams remains uncertain. Lactating C57BL/6J mice, from postpartum day (PPD) 1 to PPD 21, underwent no PS (NPS), brief PS (15 min per day, PS15), or long PS (180 min per day, PS180), followed by 21 days of chronic restraint stress (CRS). Behavioral tests were conducted, and measurements included serum PRL concentration, PRL-R expression, and AHN in the hippocampus. Dams with CRS exhibited cognitive decline, depressive- and anxiety-like behaviors, and reduced PRL secretion, correlating with lower levels of AHN. PS15 dams displayed lower levels of depressive- and anxiety-like behaviors and cognitive decline compared to NPS and PS180 dams. Significantly, PS15 dams exhibited higher levels of AHN, PRL-R expression in the hippocampus, and serum PRL concentration. This study collectively reveals reduced serum PRL and AHN in dams with cognitive decline and depressive- and anxiety-like behaviors after CRS. Brief PS confers resistance to behavioral deficits after CRS, increasing serum PRL concentration and reversing AHN decrease in dams.

催乳素(PRL)在产后阶段发挥着举足轻重的作用,尤其是在海马区--该区域密集地分布着应激激素受体,应激会显著抑制成体海马神经发生(AHN)。神经发生的减少与焦虑症和抑郁症的发病机制有关。母亲在长期压力下患抑郁症的风险会增加。因此,当务之急是研究 PRL 在产后长期应激导致的抑郁样行为中的潜在作用,并探索其潜在机制。尽管幼崽分离(PS)是一种自然的产后护理方法,但各种PS方法对哺乳母鼠的影响仍不确定。哺乳期C57BL/6J小鼠在产后第1天(PPD)至第21天(PPD 21)分别接受了无PS(NPS)、短暂PS(每天15分钟,PS15)或长时间PS(每天180分钟,PS180),然后是21天的慢性束缚应激(CRS)。进行的行为测试和测量包括血清 PRL 浓度、PRL-R 表达和海马中的 AHN。CRS母鼠表现出认知能力下降、抑郁和焦虑行为、PRL分泌减少以及AHN水平降低。与 NPS 和 PS180 母鼠相比,PS15 母鼠的抑郁和焦虑行为以及认知能力下降的程度较低。值得注意的是,PS15 母鼠表现出更高水平的 AHN、海马中 PRL-R 表达和血清 PRL 浓度。这项研究共同揭示了在CRS后出现认知能力下降、抑郁和焦虑行为的母鼠血清PRL和AHN的降低。简短的 PS 可提高血清 PRL 浓度并逆转 AHN 的下降,从而抵御 CRS 后的行为缺陷。
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引用次数: 0
Wnt Signaling Modulators Exhibit Neuroprotective Effects via Combating Astrogliosis and Balancing Synaptic Density at Early and Late Stage Temporal Lobe Epilepsy Wnt信号调节剂通过抑制星形胶质细胞增生和平衡颞叶癫痫早期和晚期的突触密度发挥神经保护作用
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04236-3
Kajal Rawat, Vipasha Gautam, Arushi Sandhu, Anil Kumar, Antika Sharma, Alka Bhatia, Lekha Saha

Temporal Lobe Epilepsy (TLE) is a severe neurological condition characterized by recurrent seizures that often do not respond well to available anti-seizure medications. TLE has been associated with epileptogenesis, a process that starts during the latent period following a neurologic insult and is followed by chronic phase. Recent research has linked canonical Wnt signaling to the pathophysiology of epileptogenesis and TLE. Our previous study demonstrated differential regulation of canonical Wnt signaling during early and late stage post status epilepticus (SE) induction. Building on these findings, our current study utilized Wnt modulators: GSK-3β inhibitor 6-bromoindirubin-3’-oxime (6-Bio) and disheveled inhibitor niclosamide and investigated their impact on canonical Wnt signaling during the early (30 days) and later stages (60 days) following SE induction. We assessed several parameters, including seizure frequency, astrogliosis, synaptic density, and neuronal counts in hippocampal tissue. We used immunohistochemistry and Nissl staining to evaluate gliosis, synaptic density, and neuronal counts in micro-dissected hippocampi. Western blotting was used to examine the expression of proteins involved in canonical Wnt/β-catenin signaling, and real-time PCR was conducted to analyze their relative mRNA expression. Wnt modulators, 6-Bio and Niclosamide were found to reduce seizure frequency and various other parameters including behavioral parameters, hippocampal morphology, astrogliosis and synaptic density at different stages of TLE.

Graphical Abstract

颞叶癫痫(TLE)是一种严重的神经系统疾病,其特点是反复发作,对现有的抗癫痫药物往往反应不佳。颞叶癫痫与癫痫发生有关,癫痫发生过程始于神经系统损伤后的潜伏期,随后进入慢性期。最近的研究将典型 Wnt 信号与癫痫发生和 TLE 的病理生理学联系起来。我们之前的研究表明,在癫痫状态(SE)诱发后的早期和晚期阶段,典型 Wnt 信号的调控存在差异。基于这些发现,我们目前的研究利用了 Wnt 调节剂:GSK-3β抑制剂6-溴靛红-3'-肟(6-Bio)和disheveled抑制剂烟酰胺,研究了它们对SE诱导后早期(30天)和晚期(60天)典型Wnt信号的影响。我们评估了几个参数,包括癫痫发作频率、星形胶质细胞增多、突触密度和海马组织中的神经元数量。我们使用免疫组化和Nissl染色来评估显微解剖海马的胶质细胞增生、突触密度和神经元数量。Western印迹法检测了参与典型Wnt/β-catenin信号转导的蛋白质的表达,实时PCR分析了它们的相对mRNA表达。研究发现,Wnt调节剂、6-Bio和Niclosamide能降低TLE不同阶段的发作频率和其他各种参数,包括行为参数、海马形态、星形胶质细胞增生和突触密度。
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引用次数: 0
Nuclear Medicine Imaging Techniques in Glioblastomas 胶质母细胞瘤的核医学成像技术。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s11064-024-04233-6
Emirhan Harbi, Michael Aschner

Glioblastomas are the most common primary malignant grade 4 tumors of the central nervous system (CNS). The treatment and management of such tumors requires a multidisciplinary approach and nuclear medicine techniques play an important role in this process. Glioblastoma, which recurs despite current treatments and becomes resistant to treatments, is among the tumors with the lowest survival rate, with a survival rate of approximately 8 months. Currently, the standard treatment of glioblastoma is adjuvant chemoradiotherapy after surgical resection. There have been many recent advances in the field of Nuclear Medicine in glioblastoma. PET scans are critical in determining tumor localization, pre-surgical planning, evaluation of post-treatment response and detection of recurrence. Advances in the treatment of glioblastoma and a better understanding of the biological characteristics of the disease have contributed to the development of nuclear medicine techniques. This review, in addition to other studies, is intended as a general imaging summary guide and includes some new expressions discovered in glioblastoma. This review discusses recent advances in nuclear medicine in glioblastoma.

胶质母细胞瘤是中枢神经系统(CNS)最常见的原发性四级恶性肿瘤。此类肿瘤的治疗和管理需要采用多学科方法,而核医学技术在这一过程中发挥着重要作用。胶质母细胞瘤在目前的治疗方法下仍会复发,并对治疗产生耐药性,是存活率最低的肿瘤之一,存活期约为 8 个月。目前,胶质母细胞瘤的标准治疗方法是手术定位后的辅助化放疗。最近,核医学在胶质母细胞瘤领域取得了许多进展。正电子发射计算机断层扫描对于确定肿瘤定位、手术前计划、评估治疗后反应和检测复发至关重要。胶质母细胞瘤治疗的进步以及对该疾病生物学特性的深入了解促进了核医学技术的发展。除其他研究外,本综述旨在作为一般成像总结指南,并包括一些在胶质母细胞瘤中发现的新表达。本综述讨论了胶质母细胞瘤核医学的最新进展。
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引用次数: 0
The Involvement of the Ventral Tegmental Area in the Electroacupuncture Alleviation of Anxiety-Like Behaviors Induced by Chronic Restraint Stress in Mice 电针缓解小鼠慢性束缚应激诱发的焦虑样行为与腹侧被盖区的关系
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-08-27 DOI: 10.1007/s11064-024-04229-2
Hua-Min Zhang, Jiang-Fan Li, Jing-Wei Zhao, Jing Shao

Emotional stress is a significant environmental risk factor for various mental health disabilities, such as anxiety. Electroacupuncture (EA) has been demonstrated to have pronounced anxiolytic effects. However, the neural mechanisms underlying these effects and their contribution to behavioral deficits remain poorly understood. Here, we addressed these issues using a classical mouse anxiety model induced by chronic restraint stress (CRS).Anxiety-like behaviors were evaluated with the open field test and elevated plus maze. Neuronal activation in various brain regions was marked using c-Fos, followed by calculations of interregional correlation to characterize a network that became functionally active following EA at the HT7 acupoint (EA-HT7). We selected the hub regions and further investigated their functions and connections in regulating anxiety-like behaviors by using a combination of chemogenetic manipulations and behavioral testing. CRS exposure induced anxiety-like behaviors. Interestingly, EA-HT7 mitigated these behavioral abnormalities. The c-Fos expression in 30 brain areas revealed a vital brain network for acupuncture responsiveness in naïve mice. Neural activity in the NAcSh (nucleus accumbens shell), BNST (bed nucleus of the stria terminalis), VMH (Ventromedial Hypothalamus), ARC (arcuate nucleus), dDG (dorsal dentate gyrus), and VTA (ventral tegmental area) was significantly altered following acupuncture. Notably, both c-Fos immunostaining and brain functional connectivity analysis revealed the significant activation of VTA following EA-HT7. Interestingly, blocking the VTA eliminated the anxiolytic effects of EA-HT7, whereas chemogenetic activation of the VTA replicated the therapeutic effects of EA-HT7. EA-HT7 has demonstrated benefits in treating anxiety and enhances brain functional connectivity. The VTA is functionally associated with the anxiolytic effects of EA-HT7.

情绪压力是导致焦虑等各种精神疾病的重要环境风险因素。电针(EA)已被证明具有明显的抗焦虑作用。然而,人们对这些效应的神经机制及其对行为缺陷的影响仍知之甚少。在此,我们使用慢性束缚应激(CRS)诱导的经典小鼠焦虑模型来解决这些问题。我们使用 c-Fos 标记了不同脑区的神经元激活情况,然后计算了区域间相关性,从而确定了 HT7 穴位 EA(EA-HT7)后功能活跃网络的特征。我们选取了这些枢纽区域,并通过化学遗传操作和行为测试相结合的方法进一步研究了它们在调节焦虑样行为中的功能和连接。CRS暴露会诱发焦虑样行为。有趣的是,EA-HT7 可减轻这些行为异常。30个脑区的c-Fos表达揭示了针灸反应的重要脑网络。针刺后,NAcSh(伏隔核)、BNST(纹状体末端床核)、VMH(内下丘脑)、ARC(弓状核)、dDG(齿状回背侧)和VTA(被盖区腹侧)的神经活动发生了显著变化。值得注意的是,c-Fos免疫染色和大脑功能连接分析均显示,针刺EA-HT7后VTA被显著激活。有趣的是,阻断VTA消除了EA-HT7的抗焦虑作用,而化学激活VTA复制了EA-HT7的治疗效果。EA-HT7在治疗焦虑症和增强大脑功能连接方面具有明显的疗效。VTA在功能上与EA-HT7的抗焦虑作用有关。
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Neurochemical Research
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