Rijpma A, Jansen D, Arnoldussen I A C, Fang X T, Wiesmann M, Mutsaers M P C, Dederen P J, Janssen C I F, Kiliaan A J
Department of Anatomy, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
J Neurodegener Dis. 2013;2013:531326. doi: 10.1155/2013/531326. Epub 2013 Jan 27.
Atherosclerosis and apolipoprotein E ε4 (APOE4) genotype are risk factors for Alzheimer's disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD.
动脉粥样硬化和载脂蛋白Eε4（APOE4）基因型是阿尔茨海默病（AD）和心血管疾病（CVD）的危险因素。这两种疾病在患病率和表现形式上存在性别差异。我们针对衰老研究了性别差异，重点关注AD和CVD的载脂蛋白E4和载脂蛋白E基因敲除（ko）小鼠模型中的认知参数。采用免疫组织化学方法对雄性和雌性载脂蛋白E4、载脂蛋白E基因敲除小鼠及野生型小鼠的突触前密度和神经发生进行了研究。中年雌性载脂蛋白E4小鼠海马齿状回内分子层的突触前密度降低。与野生型小鼠相比，中年雌性载脂蛋白E基因敲除小鼠海马神经发生有增加趋势。中年雄性小鼠在这些参数上未观察到差异。载脂蛋白E4与雌激素之间特定的有害相互作用可能是雌性载脂蛋白E4小鼠突触前密度降低的原因。在雌性载脂蛋白E基因敲除小鼠中发现的神经发生增加趋势支持了先前的研究，即突触接触和/或神经发生的暂时增加是突触功能障碍的一种补偿机制。据我们所知，尚无其他研究对衰老雌性载脂蛋白E4或载脂蛋白E基因敲除小鼠的突触前密度进行研究。载脂蛋白E基因型之间的性别特异性差异可能是AD和CVD中一些性别差异的原因。
