Accumulating evidence indicates that several of the long-term consequences of prenatal alcohol exposure (PAE) are the result of changes in the development and function of cortico-limbic structures that regulate the hypothalamic-pituitary-adrenal (HPA) axis. We hypothesize that alterations in glucocorticoid programming in the hippocampal formation underlie many of the effects of PAE on neurogenesis, synaptic plasticity and learning and memory, and that the maternal and early-life environments can modify the aberrant glucocorticoid programming. We will use an approach that overlays our drinking-in-the-dark PAE mouse model with a housing system that influences pregnant dam and offspring stress, maternal - neonate interactions and the early-life social environment using a subtle, ethologically relevant method termed the communal nest. Our preliminary studies show that communal rearing improves learning and memory in a context discrimination test, as well as reduces anxiety-like and depressive-like behaviors, in the offspring. PAE animals display deficits in a variety of hippocampal-dependent learning and memory tests, hippocampal long term potentiation (LTP) and neurogenesis. Our hypothesis, supported by published findings and preliminary data, suggest that PAE produces a feed-forward stress drive within the central control of the HPA axis. Our studies will evaluate the mitigating effects of the maternal and early-life social environment on these PAE-induced phenotypes. In addition, we will evaluate if PAE-induced changes within the extended HPA axis can be moderated by the early social environment and if the PAE-induced changes in the stress axis play a key role in these observed deficits. These studies may provide a mechanistic basis for early maternal-infant intervention as a means of mitigating the deleterious effects of PAE.

Public Health Relevance

This study will explore whether the effects of prenatal alcohol exposure can be moderated by the early social environment. Specifically, a mouse model of fetal alcohol exposure will be used to explore if communal rearing improves learning and memory and modulates stress reactivity in offspring, mitigating the effects of prenatal ethanol exposure

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
1P50AA022534-01
Application #
8600493
Study Section
Special Emphasis Panel (ZAA1-GG (50))
Project Start
Project End
Budget Start
2014-08-05
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$198,030
Indirect Cost
$66,884
Name
University of New Mexico Health Sciences Center
Department
Type
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Rodriguez, Carlos I; Davies, Suzy; Calhoun, Vince et al. (2016) Moderate Prenatal Alcohol Exposure Alters Functional Connectivity in the Adult Rat Brain. Alcohol Clin Exp Res 40:2134-2146
Marquardt, Kristin; Brigman, Jonathan L (2016) The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models. Alcohol 51:1-15
Morton, Russell A; Valenzuela, C Fernando (2016) Further characterization of the effect of ethanol on voltage-gated Ca(2+) channel function in developing CA3 hippocampal pyramidal neurons. Brain Res 1633:19-26
Kajimoto, Kenta; Valenzuela, C Fernando; Allan, Andrea M et al. (2016) Prenatal alcohol exposure alters synaptic activity of adult hippocampal dentate granule cells under conditions of enriched environment. Hippocampus 26:1078-87
Morton, Russell A; Valenzuela, C Fernando (2016) Third Trimester Equivalent Alcohol Exposure Reduces Modulation of Glutamatergic Synaptic Transmission by 5-HT1A Receptors in the Rat Hippocampal CA3 Region. Front Neurosci 10:266
Welch, J H; Mayfield, J J; Leibowitz, A L et al. (2016) Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain. Neuroscience 324:107-18
Nirgudkar, Pranita; Taylor, Devin H; Yanagawa, Yuchio et al. (2016) Ethanol exposure during development reduces GABAergic/glycinergic neuron numbers and lobule volumes in the mouse cerebellar vermis. Neurosci Lett 632:86-91
Weick, Jason P (2016) Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease. Stem Cells Int 2016:4190438
Izquierdo, A; Brigman, J L; Radke, A K et al. (2016) The neural basis of reversal learning: An updated perspective. Neuroscience :
Topper, Lauren A; Baculis, Brian C; Valenzuela, C Fernando (2015) Exposure of neonatal rats to alcohol has differential effects on neuroinflammation and neuronal survival in the cerebellum and hippocampus. J Neuroinflammation 12:160

Showing the most recent 10 out of 18 publications