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Adolescent chronic intermittent toluene inhalation dynamically regulates the transcriptome and neuronal methylome within the rat medial prefrontal cortex.
Dick, Alec L W; Zhao, Qiongyi; Crossin, Rose; Baker-Andresen, Danay; Li, Xiang; Edson, Janette; Roeh, Simone; Marshall, Victoria; Bredy, Timothy W; Lawrence, Andrew J; Duncan, Jhodie R.
Afiliación
  • Dick ALW; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
  • Zhao Q; Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
  • Crossin R; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Baker-Andresen D; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
  • Li X; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Edson J; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Roeh S; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Marshall V; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
  • Bredy TW; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Lawrence AJ; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Duncan JR; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
Addict Biol ; 26(3): e12937, 2021 05.
Article en En | MEDLINE | ID: mdl-32638524
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolueno / Corteza Prefrontal / Metilación de ADN / Proteínas de Unión al ADN / Transcriptoma Límite: Animals Idioma: En Revista: Addict Biol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tolueno / Corteza Prefrontal / Metilación de ADN / Proteínas de Unión al ADN / Transcriptoma Límite: Animals Idioma: En Revista: Addict Biol Asunto de la revista: TRANSTORNOS RELACIONADOS COM SUBSTANCIAS Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos