- Epigenetic and Transcriptional Alterations in Alcohol Use Disorder: Focus on BDNF and Opioid Systems in Brain Reward and Stress Circuits
- Palmisano, Martina <1988>
Subject
- BIO/14 Farmacologia
Description
- Prolonged exposure to alcohol and withdrawal induce a decrease of stress buffer system signaling and promotes the recruitment of several brain stress systems. The misbalance of these systems contributes to the negative emotional states (i.e. anxiety) associated with alcohol use disorder. Neuroplasticity phenomena induced by alcohol involve epigenetic modifications, such as histone modifications, which in turn regulate gene expression. In the present study, we investigated epigenetic and transcriptional alterations induced by alcohol in different paradigms of alcohol exposure. In the first part, the protein levels of histone deacetylases (HDACs) 1, 2 and 3 belonging to the class I in the caudate putamen (CPu) and prefrontal cortex (PFCx), two areas of the mesocorticostriatal circuitry, were measured in BDNF heterozygous (+/-) mice and wild type (WT) animals acutely injected with EtOH. EtOH-treated WT mice have lower protein levels of all HDAC isoforms investigated in the CPu and HDAC 3 in the PFCx, indicating that EtOH is able to modulate the epigenetic machinery. Moreover, different basal levels of HDACs class I have been detected in the BDNF +/- mice, suggesting that BDNF can be crucial in regulating epigenetic mechanisms comprising the levels of class I HDACs. In the second part, we focused on the role of dynorphin (DYN) / Îș opioid receptor (KOP) system in different model of alcohol dependence and tolerance. Results here reported indicate that alcohol induces anxiolytic effects and decrease the DYN/KOP system gene expression in the amygdala. In fact, rapid tolerance to the anxiolytic effect of EtOH can be block by the KOP receptor antagonist nor-binaltorphimine. Interestingly, epigenetic analysis in the amygdala revealed that the DYN/KOP system transcription can be mainly regulated by two histone marks, the trimethylation of lysine 27 and 4 on histone 3 (H3K27me3 and H3K4me3), during acute EtOH exposure and tolerance.
Date
- 2017-04-10
Type
- Doctoral Thesis
- PeerReviewed
Format
- application/pdf
Identifier
urn:nbn:it:unibo-20913
Palmisano, Martina (2017) Epigenetic and Transcriptional Alterations in Alcohol Use Disorder: Focus on BDNF and Opioid Systems in Brain Reward and Stress Circuits, [Dissertation thesis], Alma Mater Studiorum UniversitĂ di Bologna. Dottorato di ricerca in Scienze farmacologiche e tossicologiche, dello sviluppo e del movimento umano