Adolescent chronic intermittent toluene inhalation dynamically regulates the transcriptome and neuronal methylome within the rat medial prefrontal cortex

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.

An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality

“…However, it is difficult to exclude the impacts from benzene. As a single agent, exposure to toluene, even at low levels, has been found to change DNA methylation levels [ 254 , 255 , 256 ]. Hong et al showed that twenty-six genes are upregulated and hypomethylated, while 32 genes are downregulated and hypermethylated using in vivo samples [ 254 ]; changes in histone modifications (acetylation pattern of histones H3 and H4) [ 257 , 258 ] and microRNA expression are also observed [ 251 ].…”

Nigella Sativa Supplementations Attenuate Recognition Memory and Cellular Morphometric Impairments Induced by Toluene Administration in Mice

“…Unfortunately, it is widely used in various commercial products such as paint and printing inks and numerous industrial processes such as petrol production (Cruz, Torres-Flores & Galván 2019). Acute and chronic exposure to toluene has been shown to induce neurologic changes in animals and humans (Armenta-reséndiz et al 2019;Braunscheidel et al 2019;Demir et al 2017;Dick et al 2021;Soares et al 2020;Werder et al 2019) leading to deteriorating effects on the central nervous system. There is currently no medication for neuroprotection after toluene exposure.…”