Somatostatin and neuropeptide Y neurons undergo different plasticity in parahippocampal regions in kainic acid-induced epilepsy.
Somatostatin and neuropeptide Y neurons undergo different plasticity in parahippocampal regions in kainic acid-induced epilepsy.
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DOI：
10.1097/nen.0b013e31824d9882
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发表时间：
2012-04
影响因子：
3.2
通讯作者：
Sperk G
中科院分区：
文献类型：
--
作者：
Drexel M;Kirchmair E;Wieselthaler-Hölzl A;Preidt AP;Sperk G
在动物模型和人类颞叶癫痫模型中，海马区旁脑区包括下丘脑区、丘脑前区和副丘脑区，以及内嗅皮层产生了海马区的主要输入和输出神经元，并产生了更强的兴奋性。应用免疫组织化学和生长抑素、神经肽Y原位杂交技术，观察了海人酸致癫痫模型大鼠海马神经元的可塑性形态和神经化学变化。尽管这两个神经肽系统都包含在γ-氨基丁酸能神经元的相似亚类中，但它们在表达上经历了明显不同的变化。KA后24小时，生长抑素信使RNA(生长抑素信使RNA)在下丘脑和内嗅皮层的锥体神经元中迅速而短暂地表达。存活的生长抑素中间神经元在KA后晚期(3个月)表现为mRNA水平升高，其终末在下丘脑外分子层的标记增加；标记与自发性癫痫发作次数相关，提示癫痫发作可能触发生长抑素的表达。相反，神经肽Y在近侧下丘脑底核和外侧内嗅皮层的主神经元中持续表达，并且在几乎所有主要的兴奋通路中，神经肽Y的标记持续增加。显著的可塑性变化不同地累及两个神经肽系统，表明海马区的显著重排，推测旨在内源性癫痫保护。它们的受体可能是抗惊厥药物治疗的靶点。
Parahippocampal brain areas including the subiculum, presubiculum and parasubiculum, and entorhinal cortex give rise to major input and output neurons of the hippocampus and exert increased excitability in animal models and human temporal lobe epilepsy. Using immunohistochemistry and in situ hybridization for somatostatin and neuropeptide Y, we investigated plastic morphologic and neurochemical changes in parahippocampal neurons in the kainic acid (KA) model of temporal lobe epilepsy. Although constitutively contained in similar subclasses of γ-aminobutyric acid (GABA)-ergic neurons, both neuropeptide systems undergo distinctly different changes in their expression. Somatostatin messenger RNA (mRNA) is rapidly but transiently expressed de novo in pyramidal neurons of the subiculum and entorhinal cortex 24 hours after KA. Surviving somatostatin interneurons display increased mRNA levels at late intervals (3 months) after KA and increased labeling of their terminals in the outer molecular layer of the subiculum; the labeling correlates with the number of spontaneous seizures, suggesting that the seizures may trigger somatostatin expression. In contrast, neuropeptide Y mRNA is consistently expressed in principal neurons of the proximal subiculum and the lateral entorhinal cortex and labeling for the peptide persistently increased in virtually all major excitatory pathways of the hippocampal formation. The pronounced plastic changes differentially involving both neuropeptide systems indicate marked rearrangement of parahippocampal areas, presumably aiming at endogenous seizure protection. Their receptors may be targets for anticonvulsive drug therapy.