Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition.
Dysregulated cholesterol metabolism is a major risk factor for atherosclerosis and other late-onset disorders, such as Alzheimer's disease. The scavenger receptor, class B, type I (SR-BI) is critical in maintaining the homeostasis of cholesterol and alpha-tocopherol. SR-BI binds high-density lipoproteins (HDL) and mediates the selective transfer of cholesteryl esters and alpha-tocopherol from circulating HDL to cells. SR-BI is also involved in reverse cholesterol transport from peripheral tissues into the liver. Previous studies using SR-BI genetic knockout mice indicated that the deletion of SR-BI resulted in an accelerated onset of atherosclerosis. We hypothesized that SR-BI-dependent lipid dysregulation might disrupt brain function leading to cognitive impairment. Here, we report that very old SR-BI knockout mice show deficient synaptic plasticity (long-term potentiation) in the CA1 region of the hippocampus. Very old SR-BI KO mice also display selective impairments in recognition memory and spatial memory. Thus, SR-BI influences neural and cognitive processes, a finding that highlights the contribution of cholesterol and alpha-tocopherol homeostasis in proper cognitive function.
Chang
Eric H
EH
Burke-Cornell Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA.
Rigotti
Attilio
A
Huerta
Patricio T
PT
D000375:Aging / Q000378:metabolism* / Q000502:physiology / Q000523:psychology; D000818:Animals; D002784:Cholesterol / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D008075:Lipoproteins, HDL / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D018110:Receptors, Lipoprotein / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000378:metabolism
D008075:Lipoproteins, HDL; D018110:Receptors, Lipoprotein; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; D002784:Cholesterol; D024502:alpha-Tocopherol
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