Effects of lifestyle modifications on cognitive impairments in a mouse model of hypercholesterolemia

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• 作者：Eduardo Luiz Gasnhar Moreira^a ; ^c ; ^{eduardoluiz26@gmail.com} ; Aderbal S. Aguiar Jr.^b ; Cristiane Ribeiro de Carvalho^a ; Danú ; bia Bonfanti Santos^b ; Jade de Oliveira^b ; Andreza Fabro de Bem^b ; Joã ; o Carlos Xikota^c ; Roger Walz^c ; Marcelo Farina^b ; Rui Daniel Prediger^a ; ^c
• 关键词：Familial hypercholesterolemia ; LDL receptor knockout mice (LDLr&minus ; /&minus ; ) ; Cognitive deficits ; Physical exercise ; Probucol ; Environmental enrichment
• 刊名：Neuroscience Letters
• 出版年：2013
• 出版时间：29 April, 2013
• 年：2013
• 卷：541
• 期：Complete
• 页码：193-198
• 全文大小：538 K

文摘

Epidemiological studies indicate that high midlife plasma cholesterol levels increases the risk of Alzheimer's disease. Moreover, middle-aged familial hypercholesterolemia (FH) subjects show a particularly high incidence of mild cognitive impairments (MCI). These evidence points to hypercholesterolemia as one of the modifiable risk factors focused on prevention/treatment of cognitive deterioration. The present study draws a comparison between pharmacological (lipid-lowering drug probucol) and non-pharmacological (voluntary running wheel, RW) approaches for the management of hypercholesterolemia and cognitive impairments associated with the low-density lipoprotein receptor-deficient (LDLr^?/?) mice, a well-established rodent model of FH. We also investigated whether exposure to environmental enrichment (EE), a feasible option to increase physical activity in young mice cohort, from birth to adolescence (PN45) yields long-term behavioral changes in adult LDLr^?/? mice (PN90). We observed that both probucol and RW significantly decreased total and non-HDL plasma cholesterol levels in LDLr^?/? mice. Notably, only physical exercise mitigated the spatial memory deficits of LDLr^?/? mice. In addition, we showed that exposure to EE from birth until the adolescence did not mitigate the spatial memory deficits of adult LDLr^?/? mice in the object location task, although it induced persistent anxyolitic-like effects in the open field arena. Collectively, our results emphasize the advantages physical exercise, in comparison to lipid-lowering drugs, for the management of cognitive deficits associated with FH.