Excessive alcohol ingestion, occasionally or chronically, is co-morbid with medical disorders affecting the brain and behavior as well as other organ damage. Much of what is known about risk for and the consequence of heavy alcohol consumption, including mechanisms of organ damage, is derived from rodent studies or retrospective human accounts. This application proposes establishing a unique resource for alcohol research, a Monkey Alcohol Tissue Research Resource (MATRR). From this resource both tissue and associated bioinformatics tools will be made readily available to the wider alcohol research community. The tissue is derived from a standard protocol of ethanol self-administration in 3 species of monkeys. This resource will provide novel data for hypothesis testing relating the risk for and consequences of alcohol consumption and serve to bi-directionally bridge the gap between rodent and human studies. The basis of the MATRR is that non human primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent/day) over long periods of time (12-30 months) with concomitant pathological changes in endocrine, hepatic and central nervous system (CNS) processes. These longitudinal designs span """"""""stages of drinking"""""""" from ethanol-nai've to early alcohol exposure to chronic abuse. The CNS and peripheral organs from these animals comprise a unique translational resource for mechanistic and genetic studies of ethanol-induced pathologies. The state-of-the-art necropsy protocol will provide fresh, fixed and frozen tissue that are appropriate for ex vivo electrophysiology and neurochemical recordings, histological studies and genomic, proteomic and metabolomic approaches, respectively. The demand for, and the quality of, the tissues are already high as reflected in the number of requests and publications. Nevertheless, this resource needs further development in order to fulfill its potential as a cutting edge translational tool in alcoholism research. Thus, the primary goal of this proposal is to build the resources of this tissue bank and distribute these tissues and/or associated bioinformatics, to the broader alcohol research community.

Public Health Relevance

The research outlined in this proposal will establish a unique post-mortem tissue bank for alcohol research. Using sophisticated techniques tissues from populations of monkeys that have been chronically drinking alcohol and the related drinking and genetic information will be disseminated to the wider alcohol research community to better understand disease processes associated with alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Resource-Related Research Projects (R24)
Project #
5R24AA019431-02
Application #
8144913
Study Section
Special Emphasis Panel (ZAA1-GG (01))
Program Officer
Murray, Gary
Project Start
2010-09-20
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$797,394
Indirect Cost
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Iancu, Ovidiu D; Colville, Alexander; Walter, Nicole A R et al. (2018) On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addict Biol 23:196-205
Beattie, Matthew C; Reguyal, Christopher S; Porcu, Patrizia et al. (2018) Neuroactive Steroid (3?,5?)3-hydroxypregnan-20-one (3?,5?-THP) and Pro-inflammatory Cytokine MCP-1 Levels in Hippocampus CA1 are Correlated with Voluntary Ethanol Consumption in Cynomolgus Monkey. Alcohol Clin Exp Res 42:12-20
Alexander, Nancy J; Rau, Andrew R; Jimenez, Vanessa A et al. (2018) SNARE Complex-Associated Proteins in the Lateral Amygdala of Macaca mulatta Following Long-Term Ethanol Drinking. Alcohol Clin Exp Res 42:1661-1673
Coleman Jr, Leon G; Crews, Fulton T (2018) Innate Immune Signaling and Alcohol Use Disorders. Handb Exp Pharmacol 248:369-396
Jimenez, Vanessa A; Wang, Xiaojie; Newman, Natali et al. (2018) Detecting neurodevelopomental effects of early-gestation ethanol exposure: a non-human primate model of ethanol drinking during pregnancy. Alcohol Clin Exp Res :
Allen, Daicia C; Gonzales, Steven W; Grant, Kathleen A (2018) Effect of repeated abstinence on chronic ethanol self-administration in the rhesus monkey. Psychopharmacology (Berl) 235:109-120
Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43
Qiu, J; Wagner, E J; R√łnnekleiv, O K et al. (2018) Insulin and leptin excite anorexigenic pro-opiomelanocortin neurones via activation of TRPC5 channels. J Neuroendocrinol 30:
Cuzon Carlson, Verginia C; Grant, Kathleen A; Lovinger, David M (2018) Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset. Neuropharmacology 131:128-142
Aoun, E G; Jimenez, V A; Vendruscolo, L F et al. (2018) A relationship between the aldosterone-mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans. Mol Psychiatry 23:1466-1473

Showing the most recent 10 out of 61 publications