The central nervous system develops over a protracted period;yet, there are two times of notable vulnerability to ethanol toxicity- during fetal and adolescent development. These are also times that are of critical clinical importance because many are exposed to alcohol during fetal and adolescent life. The ongoing developmental events in the fetus and adolescent are quite different, thus the potential for ethanolinduced changes also differ. Seminal events in fetal development and during adolescence are the definition of cell fate and dendritic growth and refinement, respectively. The present study will explore the effects of ethanol on these processes by testing the hypotheses that (1) ethanol affects CNS composition by altering the fates of undetermined neuronal progenitors, (2) ethanol affects synaptic connections that are remodeled during adolescence in a time-dependent manner, and (3) plasticity in the adolescent is primed by alterations in fetal development and that such changes in the adolescent establish long-term changes in brain structure in the adult. The focus will be the cerebral cortex because it is critical for activities such as learning, memory, and executive function, acknowledged behavioral targets of ethanol. These studies will exploit transgenic mice that have a select population of neurons, pyramidal neurons in layer V, that endogenously fluoresce. Studies will determine (1) the effects of fetal ethanol exposure on neuronal fate and the contribution of the transcription factor Foxgl in that process, (2) the effects of adolescent ethanol exposure on dendritic, spine, and synaptic plasticity and the role of excitatory and inhibitory neurotransmitter systems in that plasticity, and (3) whether fetal and additional adolescent exposure combine for greater and potentially permanent changes in cortical structure. Thus, the goal of this project is to test the "alcoholism generator" hypothesis central to the DEARC- that fetal programming sets up the structure of the adult brain and that this process is exacerbated by adolescent exposure to ethanol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA017823-05
Application #
8537114
Study Section
Special Emphasis Panel (ZAA1-BB)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$87,543
Indirect Cost
$24,651
Name
State University of NY, Binghamton
Department
Type
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Gano, Anny; Doremus-Fitzwater, Tamara L; Deak, Terrence (2016) Sustained alterations in neuroimmune gene expression after daily, but not intermittent, alcohol exposure. Brain Res 1646:62-72
Doremus-Fitzwater, Tamara L; Spear, Linda P (2016) Reward-centricity and attenuated aversions: An adolescent phenotype emerging from studies in laboratory animals. Neurosci Biobehav Rev 70:121-134
Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I (2016) Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats. Behav Brain Res 310:11-9
Eade, Amber M; Youngentob, Lisa M; Youngentob, Steven L (2016) The Interaction of Ethanol Ingestion and Social Interaction with an Intoxicated Peer on the Odor-Mediated Response to the Drug in Adolescent Rats. Alcohol Clin Exp Res 40:734-42
Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián et al. (2016) Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response. Alcohol 51:89-100
Spear, Linda Patia (2016) Consequences of adolescent use of alcohol and other drugs: Studies using rodent models. Neurosci Biobehav Rev 70:228-243
Saalfield, Jessica; Spear, Linda (2016) The ontogeny of ethanol aversion. Physiol Behav 156:164-70
Santerre, J L; Kolitz, E B; Pal, R et al. (2015) Cytoplasmic phospholipase Aâ‚‚ modulation of adolescent rat ethanol-induced protein kinase C translocation and behavior. Neurochem Res 40:1023-31
Deak, Terrence; Hunt, Pamela S (2015) Early ontogeny as a unique developmental epoch for learning, memory and consequences of alcohol exposure: A Festschrift to honor the work of Dr. Norman E. Spear. Physiol Behav 148:1-5
Doremus-Fitzwater, Tamara L; Gano, Anny; Paniccia, Jacqueline E et al. (2015) Male adolescent rats display blunted cytokine responses in the CNS after acute ethanol or lipopolysaccharide exposure. Physiol Behav 148:131-44

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