@article{51e1c14be9044da48f358a3369e1a642,
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.",
keywords = "Alcoholism, Autophagy, Ethanol, Ulk1, p62",
author = "Akiko Sumitomo and Keisho Ueta and Sayaka Mauchi and Kazuko Hirai and Kouta Horike and Takatoshi Hikida and Takeshi Sakurai and Akira Sawa and Toshifumi Tomoda",
note = "Funding Information: The present study was supported by the NIH (MH-084018, MH-094268Silvio O. Conte Center, MH-069853, MH-085226, MH-088753, MH105660, and MH-092443; grants from Stanley, S-R, RUSK, NARSAD, and Maryland Stem Cell Research Fund (to A.S.); grants from Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (25116516 and 25350987 to T.S.; 15H04275, 16K14579, and 16H06568 to T.H.); grants from the Takeda Science Foundation and the Daiichi-Sankyo Foundation of Life Science (to T.H.); and by the DOD/CDMRP (W81XWH-11-1-0269) and CTF-DDI (to T.T.). In addition, the present study was partly supported by Takeda Pharmaceutical Co. Ltd. We thank the Medical Research Support Center at Kyoto University Graduate School of Medicine for access to the confocal microscope. Publisher Copyright: {\textcopyright} 2016 Elsevier Ireland Ltd and Japan Neuroscience Society",
year = "2017",
month = apr,
doi = "10.1016/j.neures.2016.12.004",
language = "English (US)",
volume = "117",
pages = "54--61",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",
}