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癫痫动物内侧延伸杏仁核中突触锌、突触小体蛋白和 MAP2 的时间变化提示反应性神经可塑性。

Timed changes of synaptic zinc, synaptophysin and MAP2 in medial extended amygdala of epileptic animals are suggestive of reactive neuroplasticity.

机构信息

Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, Argentina.

出版信息

Brain Res. 2010 Apr 30;1328:130-8. doi: 10.1016/j.brainres.2010.01.087. Epub 2010 Feb 6.

DOI:10.1016/j.brainres.2010.01.087
PMID:20144592
Abstract

Repeated seizures induce permanent alterations of the brain in experimental models and patients with intractable temporal lobe epilepsy (TLE), which is a common form of epilepsy in humans. Together with cell loss and gliosis in many brain regions, synaptic reorganization is observed principally in the hippocampus. However, in the amygdala this synaptic reorganization has been not studied. The changes in Zn density, synaptophysin and MAP(2) as markers of reactive synaptogenesis in medial extended amygdala induced by kainic acid (KA) as a model of TLE was studied. Adult male rats (n=6) were perfused at 10 days, 1, 2, 3 and 4 months after KA i.p. injection (9 mg/kg). Controls were injected with saline. The brains were processed by the Timm's method to reveal synaptic Zn and analyzed by densitometry. Immunohistochemistry was used to reveal synaptophysin and MAP(2) expression. A two-way ANOVA was used for statistics, with a P<0.05 as a significance limit. Normal dark staining was seen in all medial extended amygdala subdivisions of control animals. At 10 days post KA injection a dramatic loss of staining was observed. A slow but steady recovery of Zn density can be followed in the 4 month period studied. Parallel, from 10 days to 2 months stronger synaptophysin expression could be observed, whereas MAP(2) expression increased from 1 month with peak levels at 3-4 months. The results suggest that a process of sprouting exists in surviving neurons of medial extended amygdala after status epilepticus and that these neurons might be an evidence of a reactive synaptogenesis process.

摘要

反复癫痫发作可导致实验模型和耐药性颞叶癫痫(TLE)患者的大脑发生永久性改变,TLE 是人类常见的癫痫形式。除了许多脑区的细胞丢失和神经胶质增生外,还观察到突触重组主要发生在海马体。然而,在杏仁核中,这种突触重组尚未得到研究。本研究观察了 KA 作为 TLE 模型诱导的内侧延伸杏仁核中 Zn 密度、突触小体蛋白和 MAP(2)作为反应性突触发生的标志物的变化。成年雄性大鼠(n=6)在 KA 腹腔注射(9mg/kg)后 10 天、1、2、3 和 4 个月时进行灌注。对照组注射生理盐水。用 Timm 法处理大脑以显示突触 Zn,并通过密度测定法进行分析。免疫组织化学用于显示突触小体蛋白和 MAP(2)的表达。使用双因素方差分析进行统计学分析,显著性限为 P<0.05。所有对照组动物的内侧延伸杏仁核各亚区均可见正常的暗染色。KA 注射后 10 天观察到染色明显丢失。在研究的 4 个月期间,可以观察到 Zn 密度的缓慢但稳定的恢复。平行的,从 10 天到 2 个月可以观察到更强的突触小体蛋白表达,而 MAP(2)表达从 1 个月开始增加,在 3-4 个月达到峰值。结果表明,在癫痫持续状态后,内侧延伸杏仁核中的存活神经元中存在发芽过程,这些神经元可能是反应性突触发生过程的证据。

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