Impact of the PSA-NCAM system on pathophysiology in a chronic rodent model of temporal lobe epilepsy
Impact of the PSA-NCAM system on pathophysiology in a chronic rodent model of temporal lobe epilepsy
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DOI：
10.1016/j.nbd.2007.04.002
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发表时间：
2007-07
影响因子：
6.1
通讯作者：
A. Pekcec;M. Mühlenhoff;R. Gerardy-Schahn;H. Potschka
中科院分区：
文献类型：
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作者：
A. Pekcec;M. Mühlenhoff;R. Gerardy-Schahn;H. Potschka
聚唾液酸化是神经细胞黏附分子(NCAM)的翻译后修饰。在成人大脑中，多唾液酸化NCAM(PSA-NCAM)仅限于神经发生和神经可塑性区域，在那里PSA促进可塑性变化。由于包括神经发生在内的多种可塑性改变已被认为与癫痫的病理生理学有关，因此明确PSA-NCAM系统对癫痫及其相关合并症的发生和发展的影响是特别有意义的。在这里，我们研究了NCAM的瞬时酶促去聚唾液酸对杏仁核点燃模型的病理生理学的影响，杏仁核点燃模型是一种慢性颞叶癫痫啮齿动物模型。这些研究集中在癫痫诱导的神经发生、癫痫的进展以及与点燃相关的行为和认知变化的发展上。PSA的丢失减少了点燃过程中结合BrdU的海马区新生细胞的数量，以及位于脑门异位的新神经元的数量。基底树突的持续存在被认为是癫痫脑中新生颗粒细胞的特征。PSA的缺失增加了基底树突状细胞的数量。PSA去除引起的海马细胞增殖率和新生神经元命运的改变并不影响高兴奋性点燃网络的产生或相关的行为改变。在去除PSA和不去除PSA的大鼠中，点燃进程相似。相反，PSA的丢失增加了急性癫痫的易感性，表现为点燃前癫痫阈值的降低。这些数据表明，海马区的增殖率和异位的肺门新生神经元对癫痫网络的产生不那么关键。PSA-NCAM系统没有被证实为抗癫痫策略的目标。然而，其对异位新生神经元的影响表明，在不同的中枢神经系统损伤中，PSA-NCAM功能的调节可能是促进神经再生的一种策略。
Polysialylation is a posttranslational modification of the neural cell adhesion molecule (NCAM). In the adult brain, polysialylated NCAM (PSA-NCAM) is restricted to regions of neurogenesis and neuroplasticity, where PSA promotes plastic changes. Because a variety of plastic changes including neurogenesis have been suggested to be functionally involved in the pathophysiology of epilepsies, it is of specific interest to define the impact of the PSA-NCAM system on development and progression of this disease and associated comorbidities. Here, we studied the impact of transient enzymatic depolysialylation of NCAM on the pathophysiology in the amygdala kindling model, a chronic rodent model of temporal lobe epilepsy. The investigations focused on seizure-induced neurogenesis, seizure progression, and on the development of kindling-associated changes in behavior and cognition. Loss of PSA decreased the number of hippocampal newborn cells that incorporated BrdU during the kindling process and the number of new neurons that were ectopically located in the hilus. The persistence of basal dendrites has been suggested to be a hallmark of newborn granule cells in the epileptic brain. Loss of PSA increased the number of cells with persistent basal dendrites. The modification of the hippocampal cell proliferation rate and the fate of newborn neurons which occurred as a consequence of PSA removal did not affect the generation of a hyperexcitable kindled network or associated behavioral changes. Kindling progression was comparable in rats with and without removal of PSA. In contrast, loss of PSA increased acute seizure susceptibility as indicated by reduced seizure thresholds before kindling. The data indicate that hippocampal proliferation rates and ectoptic hilar newborn neurons are less critical for epileptic network generation. The PSA-NCAM system was not substantiated as a target for antiepileptogenic strategies. However, its impact on ectopic newborn neurons gives evidence that modulation of PSA-NCAM function may be a strategy to promote neuroregeneration in different central nervous system insults.