Lipoic acid improves neuronal insulin signalling and rescues cognitive function regulating VGlut1 expression in high-fat-fed rats: Implications for Alzheimer's disease

Biochimica Et Biophysica Acta
Manuel Rodriguez-PerdigonMaria J Ramírez

Abstract

The concept of central insulin resistance and dysfunctional insulin signalling in sporadic Alzheimer's disease (AD) is now widely accepted and diabetes is recognized as one of the main risk factors for developing AD. Moreover, some lines of evidence indicated that VGlut1 is impaired in frontal regions of AD patients and this impairment is correlated with the progression of cognitive decline in AD. The present work hypothesizes that ketosis associated to insulin resistance could interfere with the normal activity of VGlut1 and its role in the release of glutamate in the hippocampus, which might ultimately lead to cognitive deficits. High fat diet (HFD) rats showed memory impairments and both peripheral (as shown by increased fasting plasma insulin levels and HOMA index) and hippocampal (as shown by decreased activation of insulin receptor, IRS-1 and pAkt) insulin pathway alterations, accompanied by increased ketone bodies production. All these effects were counteracted by α-lipoic acid (LA) administration. VGlut1 levels were significantly decreased in the hippocampus of HFD rats, and this decrease was reversed by LA. Altogether, the present results suggest that HFD induced alterations in central insulin signalling could switch m...Continue Reading

References

Jan 1, 1993·Psychopharmacology·W J McEntee, T H Crook
Jul 21, 2000·The Journal of Clinical Investigation·J E Pessin, A R Saltiel
May 23, 2001·Progress in Neurobiology·N C Danbolt
Apr 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·S M WojcikC Rosenmund
Nov 1, 2005·Neurobiology of Aging·Carol E Greenwood, Gordon Winocur
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·S J SosciaS M de la Monte
Oct 2, 2007·The Journal of Nutritional Biochemistry·Anne M FlanaganMaria T Spicer
Jul 11, 2009·Journal of Physiology and Biochemistry·P L Prieto-HontoriaM J Moreno-Aliaga
Nov 4, 2009·Journal of Diabetes Science and Technology·Suzanne M de la Monte, Jack R Wands
Feb 17, 2010·Neuropharmacology·Paul T FrancisMitchell K Lai
Oct 6, 2010·Neuron·Narinobu JugeYoshinori Moriyama
Aug 2, 2011·Cell Metabolism·María J Moreno-AliagaMatilde Bustos
Oct 18, 2011·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·M Pilar ValdecantosJ Alfredo Martínez
Jun 6, 2012·European Journal of Nutrition·Pedro L Prieto-HontoriaMaría J Moreno-Aliaga
Nov 14, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Harsh SanchetiEnrique Cadenas
Dec 17, 2014·World Journal of Diabetes·Mario Barbagallo, Ligia J Dominguez
Feb 11, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Lina MaYun Li
Feb 11, 2015·The International Journal of Biochemistry & Cell Biology·Silvia VidaliRené G Feichtinger
May 12, 2015·Frontiers in Bioscience (Scholar Edition)·Xabier BengoetxeaMaria J Ramirez

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Citations

Nov 20, 2012·Neurobiology of Aging·Andrew B WolfJon Valla
Jun 4, 2016·Hippocampus·Manuel Rodriguez-PerdigonMaite Solas
May 8, 2020·Journal of Diabetes Research·Lin SunGuixia Wang
Mar 10, 2017·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Ghazaleh NameniMehran Mesgari Abbasi
Nov 21, 2020·Journal of Alzheimer's Disease : JAD·Julio A Flores-CuadraMaria B Carreira
Jun 6, 2017·Neurochemistry International·Scott J Koppel, Russell H Swerdlow
Jul 15, 2021·Neurotoxicity Research·Vanessa SovraniAndré Quincozes-Santos
Jul 27, 2021·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Siobhan HoscheidtSuzanne Craft
Sep 24, 2021·Journal of Neurochemistry·Md JakariaScott Ayton

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