Abstract

Alcohol dependence can cause depression by affecting hippocampal functions. Animal models of depression display dendrific atrophy and decreased spine density in hippocampal CA3 pyramidal neurons. Astrocytes have been shown to play key roles in regulafing structural and functional plasticity in neurons. Epigenetic regulation of gene expression can be modulated by histone acetylation and DNA methylation through the acfivity histone deacetylases (HDACs) and DNA methyltrasferases (DNMTs) respectively. We hypothesize that chronic ethanol and /or withdrawal induce epigenetic changes in astrocytes, affect the release of ECM proteins, inhibit neuronal plasficity in the hippocampus, and cause depressive-like behavior, effects that may be rescued by HDAC inhibifion.

Public Health Relevance

The proposed investigation of non-genetic (epigenetic) changes caused by alcohol to the DNA structure of non-neuronal brain cells, astrocytes, which may affect neuronal plasticity and may lead to the understanding of a novel mechanism of alcohol withdrawal-induced depressive behavior and to the idenfificafion of possible treatments to ameliorate ethanol-induced depression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
1P50AA022538-01
Application #
8599558
Study Section
Special Emphasis Panel (ZAA1-GG (50))
Project Start
Project End
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
1
Fiscal Year
2015
Total Cost
$186,093
Indirect Cost
$69,639

  Institution

Name
University of Illinois at Chicago
Department
Type
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612

  Publications

You, Chang; Vandegrift, Bertha; Brodie, Mark S (2018) Ethanol actions on the ventral tegmental area: novel potential targets on reward pathway neurons. Psychopharmacology (Berl) 235:1711-1726
Singh, Harinder; Wray, Nathan; Schappi, Jeffrey M et al. (2018) Disruption of lipid-raft localized G?s/tubulin complexes by antidepressants: a unique feature of HDAC6 inhibitors, SSRI and tricyclic compounds. Neuropsychopharmacology 43:1481-1491
Auta, James; Gatta, Eleonora; Davis, John M et al. (2018) Potential role for histone deacetylation in chronic diazepam-induced downregulation of ?1-GABAA receptor subunit expression. Pharmacol Res Perspect 6:e00416
You, Chang; Vandegrift, Bertha J; Zhang, Huaibo et al. (2018) Histone Deacetylase Inhibitor Suberanilohydroxamic Acid Treatment Reverses Hyposensitivity to ?-Aminobutyric Acid in the Ventral Tegmental Area During Ethanol Withdrawal. Alcohol Clin Exp Res 42:2160-2171
Satta, Rosalba; Hilderbrand, Elisa R; Lasek, Amy W (2018) Ovarian Hormones Contribute to High Levels of Binge-Like Drinking by Female Mice. Alcohol Clin Exp Res 42:286-294
Mulholland, Patrick J; Teppen, Tara L; Miller, Kelsey M et al. (2018) Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure. Alcohol Clin Exp Res 42:706-717
Moye, Laura S; Novack, Madeline L; Tipton, Alycia F et al. (2018) The development of a mouse model of mTBI-induced post-traumatic migraine, and identification of the delta opioid receptor as a novel therapeutic target. Cephalalgia :333102418777507
Zhang, Huaibo; Kyzar, Evan J; Bohnsack, John Peyton et al. (2018) Adolescent alcohol exposure epigenetically regulates CREB signaling in the adult amygdala. Sci Rep 8:10376
Savarese, Antonia; Lasek, Amy W (2018) Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3. Psychoneuroendocrinology 92:13-20
Hilderbrand, Elisa R; Lasek, Amy W (2018) Studying Sex Differences in Animal Models of Addiction: An Emphasis on Alcohol-Related Behaviors. ACS Chem Neurosci 9:1907-1916

Showing the most recent 10 out of 40 publications