The INIA Imaging Core will develop and employ tools for quantifying, cross-sectionally and longitudinally, the effects of excessive alcohol exposure at macrostructural and cellular levels in animal models of alcoholism. Accordingly, we propose that a valid animal model of human chronic alcohol consumption will produce analogous brain structural modification at the neural circuit, cellular, and neuronal morphometric levels of analysis. We hypothesize that the alcohol-related brain changes modify brain reward and executive control circuits involved in the maintenance of excessive alcohol consumption (most notably, the extended amygdala) and that further alcohol exposure results in further deterioration of inhibitory processes to resist alcohol (hypothesized to axise from limbic and frontocerebellar systems damage). This core will develop methods to examine alcohol-induced brain changes at in vivo structural (SRI and Stanford) and in vitro cellular and molecular (Indiana and Scripps) levels of analysis. In vivo neuroimaging component will develop magnetic resonance imaging (MRI) acquisition and analysis approaches for the in vivo study of brain tissue macrostructure, microstructure, and chemical composition of brain tissue. This component will develop an in vivo animal model of alcohol-induced brain changes detectable with MRI in rats bred at the Indiana Alcohol Center to drink alcohol (P); develop acquisition and analysis approaches for MR spectroscopy (MRS), MR spectroscopic imaging (MRSI), and diffusion tensor imaging (DTI) in the in vivo study of brain tissue microstructure and chemical composition of brain tissue in rats; and create tools for interested INIA sites to collect and analyze MR neuroimaging data. Cellular imaging component will provide economically efficient facilities for conducting in vitro imaging, analysis using quantitative autoradiography, carrying out in situ hybridization, performing immunocytochemical for c-fos activation and neuroanatomical identification of neurons, microdissecting discrete CNS regions, developing laser capture microdissection techniques, and initiating studies for undertaking in vivo imaging in the alcohol animal model. Neuronal quantification component will apply stereological neuronal quantification and morphometric analysis to brain systems identified with in vivo MR as affected by alcohol. Distribution of neurotransmitters and their receptors and transporters will also be probed using markers for neurotransmitter signal transduction and antibodies for immunocytochemistry or mRNA by in situ hybridization.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01AA013521-05S1
Application #
7118435
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Witt, Ellen
Project Start
2001-09-27
Project End
2006-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
5
Fiscal Year
2005
Total Cost
$45,925
Indirect Cost
Name
Sri International
Department
Type
DUNS #
009232752
City
Menlo Park
State
CA
Country
United States
Zip Code
94025
Zahr, Natalie M (2018) Peripheral TNF? elevations in abstinent alcoholics are associated with hepatitis C infection. PLoS One 13:e0191586
Sullivan, Edith V; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. JAMA Psychiatry 75:474-483
Pfefferbaum, Adolf; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. Biol Psychiatry Cogn Neurosci Neuroimaging 3:844-859
Zahr, Natalie M (2018) The Aging Brain With HIV Infection: Effects of Alcoholism or Hepatitis C Comorbidity. Front Aging Neurosci 10:56
Fama, Rosemary; Le Berre, Anne-Pascale; Hardcastle, Cheshire et al. (2017) Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism. Addict Biol :
Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2017) Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders. Neuropharmacology 122:189-200
Zahr, Natalie M; Pfefferbaum, Adolf (2017) Alcohol's Effects on the Brain: Neuroimaging Results in Humans and Animal Models. Alcohol Res 38:183-206
Perez, Xiomara A; Zhang, Danhui; Bordia, Tanuja et al. (2017) Striatal D1 medium spiny neuron activation induces dyskinesias in parkinsonian mice. Mov Disord 32:538-548
Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten et al. (2016) Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo. Psychopharmacology (Berl) 233:2675-86
Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk et al. (2016) Transient CNS responses to repeated binge ethanol treatment. Addict Biol 21:1199-1216

Showing the most recent 10 out of 61 publications