LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses
Year: 2014
Type: article
Abstract: 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.
Source: Lipids in Health and Disease
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,990
OpenAlex ID: W2170412514