Heightened seizure severity in somatostatin knockout mice
Heightened seizure severity in somatostatin knockout mice
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DOI：
10.1016/s0920-1211(01)00318-7
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发表时间：
2002-01-01
影响因子：
2.2
通讯作者：
Low, MJ
中科院分区：
文献类型：
--
作者：
Buckmaster, PS;Otero-Corchón, V;Low, MJ
颞叶癫痫患者和实验模型显示齿状回生长抑素能神经元丢失。为了确定生长抑素肽的丢失是否有助于癫痫发作，我们研究了生长抑素基因敲除小鼠中红藻氨酸诱发的癫痫发作和点燃。未观察到生长抑素敲除小鼠经历自发性癫痫发作。Timm染色，乙酰胆碱酯酶组织化学，神经肽Y，钙结合蛋白，calretinin和小清蛋白的免疫细胞化学显示生长抑素基因敲除小鼠的齿状回没有代偿性变化或发育异常。Nissl染色的肺门神经元的光学分馏计数显示野生型和生长抑素敲除小鼠中神经元的数量相似。用红藻氨酸全身性处理小鼠以诱发边缘癫痫发作。生长抑素敲除小鼠倾向于具有较短的至第5阶段癫痫发作的平均潜伏期。他们的平均最大行为癫痫评分更高，他们往往比对照组更容易死亡。在响应点燃每天电刺激的穿孔路径，更具体地挑战齿状回，平均后放电持续时间在生长抑素基因敲除小鼠稍长，但治疗的数量，5个阶段4-5癫痫发作是类似的控制。虽然我们不能排除在生长抑素基因敲除小鼠中未检测到的代偿机制的可能性，但这些发现表明生长抑素可能具有轻度抗惊厥作用，但其丢失不太可能单独解释颞叶癫痫的发作。(C)2002 Elsevier Science B. V.保留所有权利。
Patients and experimental models of temporal lobe epilepsy display loss of somatostatinergic neurons in the dentate gyrus. To determine if loss of the peptide somatostatin contributes to epileptic seizures we examined kainate-evoked seizures and kindling in somatostatin knockout mice. Somatostatin knockout mice were not observed to experience spontaneous seizures. Timm staining, acetylcholinesterase histochemistry, and immunocytochemistry for NPY, calbindin, calretinin, and parvalbumin revealed no compensatory changes or developmental abnormalities in the dentate gyrus of somatostatin knockout mice. Optical fractionator counting of Nissl-stained hilar neurons showed similar numbers of neurons in wild type and somatostatin knockout mice. Mice were treated systemically with kainic acid to evoke limbic seizures. Somatostatin knockout mice tended to have a shorter average latency to stage 5 seizures. their average maximal behavioral seizure score was higher, and they tended to be more likely to die than controls. In response to kindling by daily electrical stimulation of the perforant path, to more specifically challenge the dentate gyrus, mean afterdischarge duration in somatostatin knockout mice was slightly longer, but the number of treatments to five stage 4-5 seizures was similar to controls. Although we cannot exclude the possibility of undetected compensatory mechanisms in somatostatin knockout mice, these findings suggest that somatostatin may be mildly anticonvulsant, but its loss alone is unlikely to account for seizures in temporal lobe epilepsy. (C) 2002 Elsevier Science B.V. All rights reserved.