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Adolescent chronic intermittent toluene inhalation dynamically regulates the transcriptome and neuronal methylome within the rat medial prefrontal cortex
Author(s) -
Dick Alec L.W.,
Zhao Qiongyi,
Crossin Rose,
BakerAndresen Danay,
Li Xiang,
Edson Janette,
Roeh Simone,
Marshall Victoria,
Bredy Timothy W.,
Lawrence Andrew J.,
Duncan Jhodie R.
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12937
Subject(s) - prefrontal cortex , epigenetics , transcriptome , dna methylation , inhalation , neuroscience , hippocampus , cognition , medicine , psychology , biology , psychiatry , gene expression , gene , genetics
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.