Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway

Federico Scala; Miroslav N. Nenov; Elizabeth J. Crofton; Aditya K. Singh; Oluwarotimi Folorunso; Yafang Zhang; Brent C. Chesson; Norelle C. Wildburger; Thomas F. James; Musaad A. Alshammari; Tahani K. Alshammari; Hannah Elfrink; Claudio Grassi; James M. Kasper; Ashley E. Smith; Jonathan D. Hommel; Cheryl F. Lichti; Jai S. Rudra; Marcello D'Ascenzo; Thomas A. Green; Fernanda Laezza

doi:10.1016/j.celrep.2018.03.062

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Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway

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Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway

Federico Scala, Miroslav N. Nenov, Elizabeth J. Crofton, Aditya K. Singh, Oluwarotimi Folorunso, Yafang Zhang, Brent C. Chesson, Norelle C. Wildburger, Thomas F. James, Musaad A. Alshammari, …

Cell reports (Cambridge), Vol.23(2), pp.555-567

10/04/2018

DOI: https://doi.org/10.1016/j.celrep.2018.03.062

PMCID: PMC6150488

PMID: 29642012

Abstract

Cell Biology

Life Sciences & Biomedicine

Science & Technology

Resilience and vulnerability to neuropsychiatric disorders are linked to molecular changes underlying excitability that are still poorly understood. Here, we identify glycogen-synthase kinase 3 beta (GSK3 beta) and voltage-gated Na+ channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience and vulnerability. Transcriptomic studies in the nucleus accumbens from EC and IC rats predicted low levels of GSK3 beta and SCN8A mRNA as a protective phenotype associated with reduced excitability in medium spiny neurons (MSNs). In vivo genetic manipulations demonstrate that GSK3 beta and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3 beta prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3 beta with Nav1.6 and phosphorylation at Nav1.6(T19.36) by GSK3 beta. A GSK3 beta-Nav1.6(T19.36) competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3 beta regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity.

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Title: Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway
Creators - without role: Federico Scala - The University of Texas Medical Branch at Galveston
Miroslav N. Nenov - The University of Texas Medical Branch at Galveston
Elizabeth J. Crofton - The University of Texas Medical Branch at Galveston
Aditya K. Singh - The University of Texas Medical Branch at Galveston
Oluwarotimi Folorunso - The University of Texas Medical Branch at Galveston
Yafang Zhang - The University of Texas Medical Branch at Galveston
Brent C. Chesson - The University of Texas Medical Branch at Galveston
Norelle C. Wildburger - The University of Texas Medical Branch at Galveston
Thomas F. James - The University of Texas Medical Branch at Galveston
Musaad A. Alshammari - The University of Texas Medical Branch at Galveston
Tahani K. Alshammari - The University of Texas Medical Branch at Galveston
Hannah Elfrink - The University of Texas Medical Branch at Galveston
Claudio Grassi - Università Cattolica del Sacro Cuore
James M. Kasper - The University of Texas Medical Branch at Galveston
Ashley E. Smith - The University of Texas Medical Branch at Galveston
Jonathan D. Hommel - The University of Texas Medical Branch at Galveston
Cheryl F. Lichti - The University of Texas Medical Branch at Galveston
Jai S. Rudra - The University of Texas Medical Branch at Galveston
Marcello D'Ascenzo - Università Cattolica del Sacro Cuore
Thomas A. Green - The University of Texas Medical Branch at Galveston
Fernanda Laezza - The University of Texas Medical Branch at Galveston
Publication Details: Cell reports (Cambridge), Vol.23(2), pp.555-567
Publisher: Elsevier
Number of pages: 13
Grant note: P30ES006676 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01 MH095995; R01MH111107; R01 DA029091; T32 DA007287; T32ES007254; R01DK106229; UL1TR001439; KL2TR001441; T32DA07287 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32DA007287 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission UL1TR001439 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) P30ES006676/ES / UTMB Bench Tutorials Program: Scientific Research and Design (NIH/National Institute of Environmental Health Sciences/Department of Health and Human Services grant) Jeane B. Kempner Post-doctoral Fellowship Award R01DK106229 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01MH111107 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
Identifiers: 9946569608331
Academic Unit: King Saud University
Language: English
Resource Type: Journal article