Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model

• Published in: Nutrients 2023-07, Vol.15 (13), p.3036
• Main Authors: Hanim, Athirah, Mohamed, Isa N, Mohamed, Rashidi M P, Mokhtar, Mohd Helmy, Makpol, Suzana, Naomi, Ruth, Bahari, Hasnah, Kamal, Haziq, Kumar, Jaya
• Format: Article
• Language: English
• Subjects: Alcohol; Alcoholism; Alcoholism - metabolism; Amygdala; Animals; Carbohydrates; Correlation analysis; Drinking of alcoholic beverages; Drug dependence; Drug withdrawal; Ethanol; Gene expression; Kinases; Laboratory animals; MAP kinase; Mechanistic Target of Rapamycin Complex 2 - metabolism; mTOR; mTORC1; mTORC2; Phosphorylation; PKC epsilon; Polyclonal antibodies; Protein kinase C; Protein Kinase C-epsilon - genetics; Protein Kinase C-epsilon - metabolism; Protein kinases; Proteins; Rats; RNA, Messenger - metabolism; Rodentia; Statistical analysis; Substance Withdrawal Syndrome - metabolism; TOR protein
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15133036

Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% / ) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.