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Type: Journal article
Title: Adolescent chronic intermittent toluene inhalation dynamically regulates the transcriptome and neuronal methylome within the rat medial prefrontal cortex
Author: Dick, A.L.W.
Zhao, Q.
Crossin, R.
Baker-Andresen, D.
Li, X.
Edson, J.
Roeh, S.
Marshall, V.
Bredy, T.W.
Lawrence, A.J.
Duncan, J.R.
Citation: Addiction Biology, 2021; 26(3):e12937-1-e12937-11
Publisher: Wiley
Issue Date: 2021
ISSN: 1355-6215
Statement of
Alec L.W. Dick, Qiongyi Zhao, Rose Crossin, Danay Baker‐Andresen, Xiang Li ... Jhodie R. Duncan ... et al.
Abstract: Inhalants containing the volatile solvent toluene are misused to induce euphoria or intoxication. Inhalant abuse is most common during adolescence and can result in cognitive impairments during an important maturational period. Despite evidence suggesting that epigenetic modifications may underpin the cognitive effects of inhalants, no studies to date have thoroughly investigated toluene-induced regulation of the transcriptome or discrete epigenetic modifications within the brain. To address this, we investigated effects of adolescent chronic intermittent toluene (CIT) inhalation on gene expression and DNA methylation profiles within the rat medial prefrontal cortex (mPFC), which undergoes maturation throughout adolescence and has been implicated in toluene-induced cognitive deficits. Employing both RNA-seq and genome-wide Methyl CpG Binding Domain (MBD) Ultra-seq analysis, we demonstrate that adolescent CIT inhalation (10 000 ppm for 1 h/day, 3 days/week for 4 weeks) induces both transient and persistent changes to the transcriptome and DNA methylome within the rat mPFC for at least 2 weeks following toluene exposure. We demonstrate for the first time that adolescent CIT exposure results in dynamic regulation of the mPFC transcriptome likely relating to acute inflammatory responses and persistent deficits in synaptic plasticity. These adaptations may contribute to the cognitive deficits associated with chronic toluene exposure and provide novel molecular targets for preventing long-term neurophysiological abnormalities following chronic toluene inhalation.
Keywords: DNA methylation
inhalant misuse
volatile solvent abuse
Description: First published: 07 July 2020
Rights: © 2020 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
DOI: 10.1111/adb.12937
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