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慢性社会隔离减少成年大鼠内侧前额叶皮质小白蛋白阳性中间神经元:氟西汀和氯氮平的保护作用

Chronic social isolation reduces parvalbumin-positive interneurons in the medial prefrontal cortex of adult rats: protection by fluoxetine and clozapine
课程网址: http://videolectures.net/snc2015_todorovic_social_isolation/  
主讲教师: Nevena Todorović
开课单位: 贝尔格莱德大学
开课时间: 2015-10-01
课程语种: 英语
中文简介:
抑郁症是世界范围内导致残疾的主要原因之一。最近的研究表明,抑郁症状与GABA能系统失调之间存在联系。在精神病患者中观察到内侧前额叶皮质(mPFC)中的小白蛋白(PV)阳性GABA能中间神经元减少,mPFC是与抑郁症状密切相关的大脑区域。我们的目的是确定成年雄性Wistar大鼠长期社会隔离21天(代表抑郁的动物模型)是否会影响mPFC中央前内侧区(PrCm)、扣带皮质、1区(Cg1)、边缘前区(PrL)、边缘下区(IL)和足背皮质(DP)PV阳性中间神经元的数量。由于GABA能信号被认为是抗抑郁药或抗精神病药的潜在治疗靶点,我们研究了抗抑郁药氟西汀治疗,在21天内给予选择性5-羟色胺再摄取抑制剂(15mg/kg/天)或非典型抗精神病药氯氮平(20mg/kg/天),可防止PV阳性GABA能中间神经元最终隔离诱导的改变。免疫荧光分析结果显示,社会隔离减少了mPFC所有检查区域PV阳性中间神经元的数量。氟西汀阻止了PrCm、PrL和DP中GABA能中间神经元数量的减少,而氯氮平仅保护PrCm和PrL区域。最后,对照组大鼠服用氟西汀导致Cg1中PV阳性中间神经元数量减少,而服用氯氮平的对照组大鼠DP中PV阳性中间神经元数量减少。综上所述,长期服用氟西汀和氯氮平可对mPFC中PV阳性中间神经元产生区域特异性保护作用,使其免受慢性社会隔离的有害影响。
课程简介: Depression is one of the leading causes of disability worldwide. Recent studies have indicated that there is a link between depressive symptoms and disregulation of GABAergic system. Decrement of parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC), brain area highly implicated in depressive symptomatology, has been observed in psychiatric patients. We aimed to determine whether chronic social isolation of adult male Wistar rats for a period of 21day, which represents an animal model of depression, affects the number of PV-positive interneurons in medial precentral (PrCm) area, cingulate cortex, area 1 (Cg1), prelimbic (PrL), infralimbic (IL) area and dorsal peduncular cortex (DP) of mPFC. Since GABAergic signaling has been proposed as a potential therapeutic target for antidepressants or antipsychotics, we examined if the treatment with antidepressant fluoxetine, a selective serotonin reuptake inhibitor (15mg/kg/day) or atypical antipsychotic clozapine (20mg/kg/day) administered during the 21day may offer the protection from eventual isolation-induced alternation in PV-positive GABAergic interneurons. Results of immunofluorescence analysis revealed that social isolation reduced number of PV-positive interneurons in all examined areas of mPFC. Fluoxetine prevented reduction of number of these GABAergic interneurons in PrCm, PrL and DP, while clozapine only protected PrCm and PrL area. Finally, fluoxetine administration to control rats caused decrement in number of PV-positive interneurons in Cg1, while clozapine-treated control animals exhibited reduced number of these interneurons in DP. In summary, chronic administration of fluoxetine and clozapine showed area specific protection of PV-positive interneurons in the mPFC from deleterious effect of chronic social isolation.
关 键 词: 抑郁症; 残疾; GABA能系统失调
课程来源: 视频讲座网
数据采集: 2021-12-14:nkq
最后编审: 2021-12-14:nkq
阅读次数: 101