Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice.

A Rijpma,I A C Arnoldussen,P J Dederen,X T Fang,D Jansen,M Wiesmann,C I F Janssen,M P C Mutsaers,A J Kiliaan

doi:10.1155/2013/531326

A Rijpma, I A C Arnoldussen + Show 7 more

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https://doi.org/10.1155/2013/531326

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Abstract

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.

Highlights

Western society is currently faced with an increasing incidence of vascular diseases such as hypercholesterolemia and atherosclerosis, mainly as a consequence of unhealthy lifestyle habits, an increase in obesity, and an aging population
Post hoc analysis revealed a signi cant decrease in the number of synaptophysin-immunoreactive presynaptic boutons (SIPBs) in female apoE4 mice compared with female wildtype (WT) mice (WT: MM MMMM, SEM =4.67; apoE4: MM MMM.28, SEM = 2.91; PP P PPPP, Figure 3). ere were no signi cant differences in the number of SIPBs in the cortex or in other regions of the hippocampus
In female apoE4 mice, we found a decrease in the number of synaptophysin-immunoreactive presynaptic boutons (SIPBs) in the inner molecular layer (IML) of the dentate gyrus compared with controls

Summary

Introduction

Western society is currently faced with an increasing incidence of vascular diseases such as hypercholesterolemia and atherosclerosis, mainly as a consequence of unhealthy lifestyle habits, an increase in obesity, and an aging population. Vascular diseases and obesity are risk factors for disorders that affect cognitive function such as diabetes mellitus, stroke, vascular dementia, and Alzheimer’s disease (AD) [1, 2]. Sex differences exist in both AD and cardiovascular disease (CVD). While women have a higher risk for AD, men are generally more affected by CVD [3]. Men are more prone to develop high serum cholesterol levels at a younger age than (premenopausal) women [4, 5]. Most of these sex differences disappear, when women reach menopause, when they equal and even surpass men in the prevalence of CVD [3, 6]. While men have thicker atherosclerotic plaques in the large coronary arteries, women tend to have more diffuse plaques that impair the smaller microvasculature [4, 5, 7]

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