Ulk1 protects against ethanol-induced neuronal stress and cognition-related behavioral deficits. (April 2017)

• Record Type: Journal Article
• Authors: Sumitomo, Akiko; Ueta, Keisho; Mauchi, Sayaka; Hirai, Kazuko; Horike, Kouta; Hikida, Takatoshi; Sakurai, Takeshi; Sawa, Akira; Tomoda, Toshifumi
• Is Part Of: Neuroscience research. Volume 117(2017:Apr.)
• Page Start: 54
• Page End: 61
• Publication Date: 2017-04
• Subjects: Alcoholism -- Autophagy -- Ethanol -- Ulk1 -- p62; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2016.12.004
• Languages: English
• ISSNs: 0168-0102

Abstract

Abstract: Alcoholism is a psychiatric condition that develops through neuroadaptations in response to neuronal stresses caused by chronic ethanol intake. Neurons can adapt to ethanol-induced metabolic changes by activating cellular protective mechanisms, including autophagy. Here we show that expression of Ulk1, a gene critical to the regulation of autophagy, was affected in the prefrontal cortex (PFC) of mice following chronic intermittent ethanol (CIE) exposure. Consequently, overall levels of Ulk1 activity in the PFC were downregulated, leading to accumulation of p62, a protein that serves as a target for autophagic degradation. In addition, Ulk1 -null mice demonstrated decline in the exploratory activity, deficits in the ability to recognize novel objects following CIE exposure, and reduced rate of voluntary ethanol drinking. The data suggest the neuroprotective role for Ulk1-mediated autophagy in the suppression of neuropsychiatric manifestation during ethanol exposure. Highlights: Chronic ethanol intake reduces Ulk1 activity in neurons of the prefrontal cortex. Chronic ethanol intake attenuates neuronal autophagy. Loss of Ulk1 impairs cognition-related behaviors and voluntary ethanol drinking.