LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses

Lipids in Health and Disease

Rong Huang¹  Pin Wang¹  Wen-qing Xia¹  Yang Yuan¹  Yan Huang²  Shao-hua Wang¹ 

[1] Department of Endocrinology, ZhongDa Hospital of Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, PR China;Department of Endocrinology, YanCheng First People’s Hospital, No.16 YueHe Road, YanCheng 224005, PR China

关键词: Apoptosis;    Synapse;    Cognition;    LDL receptor knock-out;   

Others  :  1145602
DOI  :  10.1186/1476-511X-13-175

 received in 2014-08-18, accepted in 2014-11-11,  发布年份 2014

【 摘 要 】

Background

Evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction. The low-density lipoprotein receptor (LDLR) is well-known for its role in regulating cholesterol metabolism. Whether LDLR involved in this impaired cognition and the potential mechanisms that underlie this impairment are unknown.

Methods

Twelve-month-old Ldlr-/- mice (n = 10) and wild-type littermates C57BL/6 J (n = 14) were subjected to the Morris water maze test. At 1 week after completion of the behavioural testing, all of the animals were sacrificed for analysis of synaptic and apoptotic markers.

Results

The plasma cholesterol concentration of Ldlr-/- mice was increased moderately when compared with C57BL/6 J mice (P < 0.05). Behavioural testing revealed that Ldlr-/- mice displayed impaired spatial memory, and moreover, the expression levels of synaptophysin and the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and dentate gyrus were decreased (all P < 0.05). Ultrastructural changes in the dentate gyrus were observed using transmission electron microscopy. Furthermore, apoptosis in the hippocampus of Ldlr-/- mice was revealed based on elevation, at both the mRNA and protein levels, of the ratio of Bax/Bcl-2 expression (all P < 0.05)and an increase in activated-caspase3 protein level (P < 0.05).

Conclusion

LDLR deficiency contributes to impaired spatial cognition. This most likely occurs via negative effects that promote apoptosis and synaptic deficits in the hippocampus.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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