title: Ulk1 protects against ethanol-induced neuronal stress and cognition-related behavioral deficits.
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.
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sumitomo
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Keisho
authors.initials: K
authors.lastname: Ueta
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mauchi
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Kouta
authors.initials: K
authors.lastname: Horike
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hikida
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Johns Hopkins University School of Medicine, Dept. of Psychiatry, Baltimore, MD, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Kyoto University Graduate School of Medicine, Medical Innovation Center, Kyoto, Japan; University of Toronto, Centre for Addiction and Mental Health, Toronto, ON, Canada. Electronic address: toshifumi.tomoda@camh.ca.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tomoda
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology*; D015536:Down-Regulation; D000431:Ethanol / Q000494:pharmacology*; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D000431:Ethanol; D000071189:Autophagy-Related Protein-1 Homolog; C112444:Ulk1 protein, mouse
keywords: Alcoholism; Autophagy; Ethanol; Ulk1; p62