mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Jordan B JahrlingVeronica Galvan

Abstract

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR-/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, o...Continue Reading

References

Jul 1, 1991·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A J MartinR S Frackowiak
May 1, 1984·Journal of Neuroscience Methods·R Morris
May 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·K J Williams, I Tabas
Feb 24, 1998·Stroke; a Journal of Cerebral Circulation·L H KullerR Bhadelia
Mar 22, 2000·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·T Q DuongS G Kim
Aug 5, 2000·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·J H Jensen, R Chandra
Mar 21, 2001·Behavioral Neuroscience·K M Frick, J Berger-Sweeney
Mar 6, 2002·Circulation·Peter LibbyAttilio Maseri
Mar 13, 2002·Circulation·Johann W AuerBernd Eber
May 1, 2002·Annals of Plastic Surgery·W Tomasz MajewskiArturo Aguillon
Aug 2, 2003·Cardiovascular Radiation Medicine·Ron WaksmanDavid Hellinga
Jun 5, 2004·Neurochemical Research·Marcin SadowskiThomas Wisniewski
Jun 12, 2004·Current Atherosclerosis Reports·José A Luchsinger, Richard Mayeux
Aug 25, 2005·Alzheimer Disease and Associated Disorders·John C Morris
Oct 12, 2005·Archives of Neurology·Miia KivipeltoAulikki Nissinen
Oct 19, 2006·Journal of Biomedicine & Biotechnology·Leonel RojoRicardo B Maccioni
Jun 2, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Susanne ZadelaarTeake Kooistra
Oct 24, 2007·Metabolism: Clinical and Experimental·Nicholas F BrownGerman Perdomo
Dec 21, 2007·Nature Reviews. Neuroscience·Charles H HillmanArthur F Kramer
May 10, 2008·Behavioural Brain Research·Gregory A ElderJoseph D Buxbaum
Aug 5, 2008·The American Journal of Geriatric Pharmacotherapy·Howard FillitAndrea Zuckerman
Oct 14, 2008·Immunity·Thomas WeichhartMarcus D Säemann
Mar 24, 2009·Annual Review of Immunology·Elena Galkina, Klaus Ley
Jul 10, 2009·Nature·David E HarrisonRichard A Miller
Oct 27, 2009·Molecular Neurodegeneration·Sonia FranciosiGregory A Elder
Mar 18, 2011·Psychoneuroendocrinology·Milena GirottiDavid A Morilak
Apr 30, 2011·Journal of Applied Physiology·Michelle W VossArthur F Kramer
Jul 23, 2011·Stroke; a Journal of Cerebral Circulation·Philip B GorelickUNKNOWN American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Counci
Nov 4, 2011·Nature Reviews. Neuroscience·Berislav V Zlokovic
May 17, 2012·Aging Cell·John E WilkinsonRichard A Miller

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Citations

Mar 24, 2018·Journal of Cellular and Molecular Medicine·Sunlei PanHangyuan Guo
Jan 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Candice E Van SkikeVeronica Galvan
Mar 9, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Gabor A FulopZoltan Ungvari
Nov 7, 2019·Aging Cell·Candice E Van SkikeVeronica Galvan
Mar 15, 2019·Aging·Candice E Van Skike, Veronica Galvan
Aug 7, 2020·Aging·Candice E Van Skike, Veronica Galvan
Apr 25, 2018·Journal of Alzheimer's Disease : JAD·Sinian LiBin Zhao
Oct 26, 2018·Circulation Research·Zoltan UngvariAnna Csiszar
Oct 11, 2020·GeroScience·Ramasamy SelvaraniArlan Richardson
Jan 11, 2021·CNS Neuroscience & Therapeutics·Chao LiYi Yang
Nov 5, 2020·Mechanisms of Ageing and Development·Samir Morsli, Ilaria Bellantuono

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Methods Mentioned

BETA
blood collection
ELISA
PCR

Software Mentioned

Matlab
ARRIVE
STIMULATE
GraphPad Prism

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