Insulin receptor sensitization restores neocortical excitation/inhibition balance in a mouse model of autism

Molecular Autism
Fu-Sun Lo, Reha S Erzurumlu

Abstract

Met receptor tyrosine kinase regulates neurogenesis, differentiation, migration, connectivity, and synaptic plasticity. The human Met gene has been identified as a prominent risk factor for autism spectrum disorder (ASD). Met gene-altered mice serve as useful models for mechanistic studies of ASD. Inactivation of Met in excitatory cortical neurons in mice (Emx1 cre /Met flox mice) yields a phenotype in which significantly decreased GABAA receptor-mediated inhibition shifts the excitation/inhibition (E/I) balance toward excitation in the somatosensory cortex. Further, unlike that seen in wild-type mice, insulin does not increase inhibition in the mutant cortex, suggesting that one of the consequences of kinase inactive Met gene could be desensitization of insulin receptors. To test this hypothesis, we investigated the effects of insulin receptor sensitizer, pioglitazone, on inhibition in the somatosensory thalamocortical circuitry. We used whole-cell patch clamp electrophysiology and analyzed excitatory and inhibitory responses of cortical layer IV excitatory cells following stimulation of their thalamic input in thalamocortical pathway intact brain slices. We applied insulin alone and insulin + a thiazolidinedione, pioglitazon...Continue Reading

References

Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·G E HomanicsR W Olsen
Jun 20, 2003·Journal of Neurophysiology·Michael BeierleinBarry W Connors
Nov 11, 2003·Genes, Brain, and Behavior·J L R Rubenstein, M M Merzenich
Mar 10, 2005·Neuroscience Letters·Abdeslem El IdrissiCarl Dobkin
Apr 2, 2005·The Journal of Comparative Neurology·Li-Jen LeeReha S Erzurumlu
Jan 9, 2007·Journal of Neuroinflammation·Marvin BorisDouglas L Feinstein
Mar 6, 2007·Medical Hypotheses·Enzo EmanueleFrancesco Barale
May 18, 2010·Neuropharmacology·Daniel C AduseiDavid R Hampson
Jul 29, 2010·Journal of Neurodevelopmental Disorders·Nadine GogollaTakao K Hensch
Apr 15, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shenfeng QiuGordon M G Shepherd
Nov 17, 2011·Cold Spring Harbor Perspectives in Biology·Gina Turrigiano
May 4, 2012·Expert Opinion on Pharmacotherapy·Carolyn A Doyle, Christopher J McDougle
Sep 21, 2013·Journal of Neurophysiology·Fu-Sun LoReha S Erzurumlu
Dec 11, 2013·Frontiers in Pharmacology·Marina Kawaguchi-Suzuki, Reginald F Frye
Feb 18, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Haim Werner, Derek LeRoith
Mar 19, 2014·Journal of the American Geriatrics Society·Stephen ReadMark Biscow
Jul 3, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael V AccardiDerek Bowie
Apr 1, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fu-Sun LoElizabeth M Powell
Oct 5, 2016·Current Alzheimer Research·David Hsu, Gad A Marshall
Nov 26, 2016·Expert Opinion on Investigational Drugs·Daniela Galimberti, Elio Scarpini
Nov 28, 2016·Journal of Neurochemistry·Matthias Gralle
Jan 7, 2017·Current Topics in Developmental Biology·A B Mihalas, R F Hevner

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Citations

May 28, 2019·Expert Opinion on Drug Discovery·Kathryn K ChadmanRobert Feingold
Mar 13, 2020·Neurochemical Research·Yan YanHaibing Yu
Oct 21, 2020·Genes·Madiha KhalidGhazala Kaukab Raja
Aug 3, 2021·Frontiers in Cellular Neuroscience·Xiaona WangQi Wang

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Methods Mentioned

BETA
transgenic

Software Mentioned

PULSE ( HEKA )
MiniAnalysis
R

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