Effetto dell’etanolo sullo stato di metilazione del gene che codifica per la neurotrofina “Brain-Derived Neurotrophic Factor”
type: CreativeWork
description: Alcohol addiction is thought to depend on molecular and cellular adaptations in the brain that result from chronic drug exposure (Fitzgerald and Nestler, 1995 ). This suggests that chronic alcohol abuse involves stable changes in the brain at the molecular and cellular levels responsible for long-lasting alterations in behavior. One of the candidate molecules involved in such mechanisms is brain-derived neurotrophic factor (BDNF). Aberrant regulation of BDNF has been implicated in the development of psychiatric disorders, including schizophrenia, depression, anxiety and alcohol addiction (Moonat et al., 2010). Multiple actions of ethanol on BDNF gene expression and signalling have been described. Nevertheless the considerable complexity within the BDNF gene itself and the multiple mRNAs encoded by up to 9 potential exons is further complicated because of its epigenetic regulation by methylation of BDNF promoters. The knowledge of the promoter that may be differentially regulated during various states of ethanol exposure and a detailed analysis of the effects of different ethanol exposure treatments on mRNA expression is required to understand the biological basis of addiction. This will lead to more effective treatments and eventually to cures and preventive measures to treat alcohol addiction. The aim of this work was to evaluate the effects of ethanol on CpG islands of BDNF exon IX gene in regulating its expression, both “in vivo” and “in vitro”. Rat cerebellar granule cells in culture were exposed to acute ethanol, chronic ethanol or ethanol withdrawal. Our results demonstrate that ethanol exposure increases, the abundance of BDNF exon IX transcript in the three different treatment conditions. We then tested the ability of acute ethanol to alter exon IX methylation by using MSP PCR. Similarly to the effect induced by the two DNA methylation inhibitors, zebularine and RG-108, exposure of cultured neurons to 100 mM ethanol for 3h significantly increased the unmethy…
abstract: Alcohol addiction is thought to depend on molecular and cellular adaptations in the brain that result from chronic drug exposure (Fitzgerald and Nestler, 1995 ). This suggests that chronic alcohol abuse involves stable changes in the brain at the molecular and cellular levels responsible for long-lasting alterations in behavior. One of the candidate molecules involved in such mechanisms is brain-derived neurotrophic factor (BDNF). Aberrant regulation of BDNF has been implicated in the development of psychiatric disorders, including schizophrenia, depression, anxiety and alcohol addiction (Moonat et al., 2010). Multiple actions of ethanol on BDNF gene expression and signalling have been described. Nevertheless the considerable complexity within the BDNF gene itself and the multiple mRNAs encoded by up to 9 potential exons is further complicated because of its epigenetic regulation by methylation of BDNF promoters. The knowledge of the promoter that may be differentially regulated during various states of ethanol exposure and a detailed analysis of the effects of different ethanol exposure treatments on mRNA expression is required to understand the biological basis of addiction. This will lead to more effective treatments and eventually to cures and preventive measures to treat alcohol addiction. The aim of this work was to evaluate the effects of ethanol on CpG islands of BDNF exon IX gene in regulating its expression, both “in vivo” and “in vitro”. Rat cerebellar granule cells in culture were exposed to acute ethanol, chronic ethanol or ethanol withdrawal. Our results demonstrate that ethanol exposure increases, the abundance of BDNF exon IX transcript in the three different treatment conditions. We then tested the ability of acute ethanol to alter exon IX methylation by using MSP PCR. Similarly to the effect induced by the two DNA methylation inhibitors, zebularine and RG-108, exposure of cultured neurons to 100 mM ethanol for 3h significantly increased the unmethy…
author: FLORIS, GABRIELE
language: ita
keywords: BDNF, DNA methylation, etanolo, ethanol, metilazione del DNA, Settore BIO/11 - Biologia Molecolare
date published: 2014-05-08
date modified: 2026-07-24T01:30:07Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

PropertyValue
property ID: Handle
value: http://hdl.handle.net/11584/266470