Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes

Molecular Autism
Joana GonçalvesMiguel Castelo-Branco

Abstract

Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased γ-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1+/- mouse. Cortical and striatal GABA/glutamate ratios wer...Continue Reading

References

Jan 1, 1987·Annals of the New York Academy of Sciences·P A Bottomley
May 20, 1999·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·I TkácR Gruetter
Feb 17, 2001·American Journal of Medical Genetics·K North
Jun 19, 2001·NMR in Biomedicine·S W Provencher
Feb 14, 2003·Current Neurology and Neuroscience Reports·Tena L Rosser, Roger J Packer
Dec 23, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kimberly Jett, Jan M Friedman
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Carrie ShilyanskyAlcino J Silva
Jan 1, 2005·Current Neuropharmacology·David W Volk, David A Lewis
Feb 15, 2013·Journal of Neurodevelopmental Disorders·Inês R ViolanteMiguel Castelo-Branco
Sep 23, 2014·Nature Neuroscience·Andrei I MoloshAnantha Shekhar
Dec 2, 2014·Cortex; a Journal Devoted to the Study of the Nervous System and Behavior·Maria J RibeiroMiguel Castelo-Branco
Dec 6, 2014·Journal of Autism and Developmental Disorders·Shruti GargJonathan Green
Jul 28, 2016·Biological Psychiatry·Eunee LeeEunjoon Kim
Jul 31, 2016·Neurology·Inês R ViolanteMiguel Castelo-Branco
Aug 16, 2016·Journal of Neurodevelopmental Disorders·Shruti GargUNKNOWN Northern UK NF1 Research Network
Feb 19, 2017·Neuroscience Bulletin·Anne MasiAdam J Guastella

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Citations

Mar 24, 2018·Journal of Neurodevelopmental Disorders·Gilberto SilvaMiguel Castelo-Branco
Apr 17, 2020·Autism Research : Official Journal of the International Society for Autism Research·Tamar KolodnyScott O Murray
Jun 21, 2018·Frontiers in Genetics·Carolina Torres-Rojas, Byron C Jones
May 28, 2019·The British Journal of Radiology·Russell G PortTimothy Pl Roberts
Jul 4, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Taylor F SmithMaria T Acosta
May 9, 2021·Journal of Autism and Developmental Disorders·Gorana PobricShruti Garg
May 30, 2021·Journal of Neurodevelopmental Disorders·Jannath Begum-AliUNKNOWN STAARS and EDEN Teams
Jul 21, 2021·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Eirene I GermanidisJan E Timmermann

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Methods Mentioned

BETA
Protein Extraction
electrophoresis

Software Mentioned

LCModel
GraphPad
NIH
GraphPad Prism
MAPSHIM
NIH ImageJ
Fiji ImageJ

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