Wong-Goodrich Sarah J E, Mellott Tiffany J, Glenn Melissa J, Blusztajn Jan K, Williams Christina L
Department of Psychology and Neuroscience, Duke University, Durham, NC 27708, USA.
Neurobiol Dis. 2008 May;30(2):255-69. doi: 10.1016/j.nbd.2008.01.008. Epub 2008 Feb 16.
Prenatal choline supplementation (SUP) protects adult rats against spatial memory deficits observed after excitotoxin-induced status epilepticus (SE). To examine the mechanism underlying this neuroprotection, we determined the effects of SUP on a variety of hippocampal markers known to change in response to SE and thought to underlie ensuing cognitive deficits. Adult offspring from rat dams that received either a control or SUP diet on embryonic days 12-17 were administered saline or kainic acid (i.p.) to induce SE and were euthanized 16 days later. SUP markedly attenuated seizure-induced hippocampal neurodegeneration, dentate cell proliferation, and hippocampal GFAP mRNA expression levels, prevented the loss of hippocampal GAD65 protein and mRNA expression, and altered growth factor expression patterns. SUP also enhanced pre-seizure hippocampal levels of BDNF, NGF, and IGF-1, which may confer a neuroprotective hippocampal microenvironment that dampens the neuropathological response to and/or helps facilitate recovery from SE to protect cognitive function.
产前补充胆碱(SUP)可保护成年大鼠免受兴奋性毒素诱导的癫痫持续状态(SE)后出现的空间记忆缺陷。为了研究这种神经保护作用的潜在机制,我们确定了SUP对多种海马标志物的影响,这些标志物已知会因SE而发生变化,并被认为是随后认知缺陷的基础。在胚胎第12 - 17天接受对照或SUP饮食的大鼠母鼠的成年后代,经腹腔注射生理盐水或海藻酸以诱导SE,并在16天后实施安乐死。SUP显著减轻了癫痫发作诱导的海马神经变性、齿状细胞增殖和海马GFAP mRNA表达水平,防止了海马GAD65蛋白和mRNA表达的丧失,并改变了生长因子表达模式。SUP还提高了癫痫发作前海马中BDNF、NGF和IGF - 1的水平,这可能赋予一种神经保护性的海马微环境,减轻对SE的神经病理反应和/或有助于促进从SE中恢复,从而保护认知功能。