title: Age-related influence of the HDL receptor SR-BI on synaptic plasticity and cognition.
abstract: 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.
authors: Burke-Cornell Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, White Plains, NY 10605, USA.
authors: Eric H
authors: EH
authors: Chang
authors: Attilio
authors: A
authors: Rigotti
authors: Patricio T
authors: PT
authors: Huerta
mesh_terms: 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
chemical_list: 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
references: Annu Rev Neurosci. 1989;12:13-31
references: 2648947
references: N Engl J Med. 1989 Nov 9;321(19):1311-6
references: 2677733
references: Neurobiol Aging. 1990 Nov-Dec;11(6):601-7
references: 1704106
references: Science. 1992 Oct 16;258(5081):468-71
references: 1411543
references: Brain Res. 1993 Feb 26;604(1-2):173-9
references: 8457845
references: Nature. 1993 Aug 19;364(6439):723-5
references: 8355787
references: Hum Mutat. 1994;4(3):178-94
references: 7833947
references: Neurology. 1995 Jun;45(6):1092-6
references: 7783869
references: Exp Neurol. 1995 Dec;136(2):107-22
references: 7498401
references: Biochem Mol Biol Int. 1995 Sep;37(1):133-40
references: 8653075
references: Science. 1996 Jan 26;271(5248):518-20
references: 8560269
references: Science. 1996 May 3;272(5262):685-8
references: 8614828
references: Neuron. 2000 Feb;25(2):473-80
references: 10719900
references: Annu Rev Biochem. 1999;68:523-58
references: 10872459
references: Neurobiol Dis. 2000 Aug;7(4):321-31
references: 10964604
references: J Neurochem. 2000 Dec;75(6):2563-73
references: 11080210
references: Lancet. 2000 Nov 11;356(9242):1627-31
references: 11089820
references: Ann N Y Acad Sci. 2000;924:104-11
references: 11193786
references: AJNR Am J Neuroradiol. 2001 Jan;22(1):119-27
references: 11158897
references: Curr Opin Lipidol. 2001 Apr;12(2):105-12
references: 11264981
references: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5856-61
references: 11296263
references: Behav Brain Res. 2001 Sep 28;124(1):33-46
references: 11423164
references: Neurology. 2001 Jun 26;56(12):1683-9
references: 11425934
references: J Lipid Res. 2001 Jul;42(7):1143-51
references: 11441143
references: FASEB J. 2001 Aug;15(10):1858-60
references: 11481254
references: Nat Cell Biol. 2001 Oct;3(10):905-12
references: 11584272
references: Neuron. 2001 Oct 25;32(2):181-4
references: 11683989
references: J Clin Invest. 2001 Dec;108(11):1717-22
references: 11733567
references: Blood. 2002 Mar 1;99(5):1817-24
references: 11861300
references: Science. 1996 Oct 4;274(5284):99-102
references: 8810256
references: Cell. 1996 Dec 27;87(7):1327-38
references: 8980238
references: JAMA. 1997 Mar 12;277(10):813-7
references: 9052711
references: Lancet. 1997 Jan 18;349(9046):151-4
references: 9111537
references: J Biol Chem. 1997 Jul 11;272(28):17551-7
references: 9211901
references: Ann N Y Acad Sci. 1997 Sep 26;826:128-46
references: 9329686
references: Hippocampus. 1997;7(5):549-58
references: 9347351
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12610-5
references: 9356497
references: J Biol Chem. 1997 Nov 28;272(48):30178-84
references: 9374499
references: J Biol Chem. 1997 Dec 26;272(52):33068-76
references: 9407090
references: Neuroepidemiology. 1998;17(1):14-20
references: 9549720
references: J Biol Chem. 1998 May 15;273(20):12161-8
references: 9575163
references: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6460-4
references: 9600988
references: J Biol Chem. 1998 Dec 4;273(49):32920-6
references: 9830042
references: J Biol Chem. 1999 Jan 22;274(4):2366-71
references: 9891004
references: Neuroscience. 1999;92(4):1273-86
references: 10426483
references: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9322-7
references: 10430941
references: Neuroreport. 2004 Dec 3;15(17):2655-8
references: 15570172
references: Neurobiol Aging. 2005 Mar;26(3):355-61
references: 15639314
references: Ann N Y Acad Sci. 2004 Dec;1031:127-42
references: 15753140
references: J Neurol Sci. 2005 Mar 15;229-230:233-40
references: 15760645
references: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3410-5
references: 16492745
references: J Nutr. 2002 Mar;132(3):443-9
references: 11880569
references: J Neurochem. 2002 Jun;81(5):1084-91
references: 12065621
references: J Neurochem. 2001 Jan;76(2):391-400
references: 11208902
references: J Mol Neurosci. 2002 Aug-Oct;19(1-2):155-61
references: 12212773
references: Glia. 2002 Nov;40(2):195-205
references: 12379907
references: Ann N Y Acad Sci. 2002 Nov;977:367-75
references: 12480774
references: Arch Neurol. 2003 Jan;60(1):29-35
references: 12533085
references: Nat Neurosci. 2003 Apr;6(4):345-51
references: 12658281
references: Philos Trans R Soc Lond B Biol Sci. 2003 Apr 29;358(1432):821-8
references: 12740129
references: Endocr Rev. 2003 Jun;24(3):357-87
references: 12788804
references: J Biol Chem. 2003 Jun 27;278(26):23699-705
references: 12639961
references: Am J Pathol. 2003 Dec;163(6):2155-64
references: 14633589
references: Neuron. 2004 Jan 8;41(1):7-10
references: 14715130
references: Arterioscler Thromb Vasc Biol. 2004 May;24(5):806-15
references: 14764421
references: J Nutr Biochem. 2004 May;15(5):252-60
references: 15135148
references: J Clin Pharm Ther. 2004 Jun;29(3):209-13
references: 15153082
references: J Biol Chem. 2004 Aug 13;279(33):34674-81
references: 15148325
references: Immunity. 2004 Aug;21(2):179-88
references: 15308099
references: Neuron. 2004 Sep 2;43(5):633-45
references: 15339646
references: Stroke. 2004 Nov;35(11 Suppl 1):2623-7
references: 15375298
references: Psychopharmacologia. 1968 Sep 20;13(3):222-57
references: 5679627
references: J Physiol. 1973 Jul;232(2):331-56
references: 4727084
references: Nature. 1982 Jun 24;297(5868):681-3
references: 7088155
references: Nature. 1986 Feb 27-Mar 5;319(6056):774-6
references: 2869411
references: Lab Invest. 1989 Mar;60(3):455-61
references: 2927083