The development of cerebral cortex is profoundly disrupted by the prenatal exposure to ethanol. These defects provide the basis for a variety of disorders including mental retardation and motor dysfunction which characterize fetal alcohol syndrome (FAS). The initial two years of this project were devoted to surveying the effects of prenatal ethanol exposure on neuronal ontogeny. This proposal outlines a more detailed examination of the effects of prenatal exposure to ethanol on the ontogeny of neurons and glia in motor-somatosensory cortex. Three processes constitute cellular ontogeny; proliferation, migration, and differentiation. The effects of prenatal exposure to ethanol on each of these phases will be examined. The proliferation of cortical neurons and glia will be assessed using double-labeling immunocytochemical and autoradiographic techniques which makes it possible to trace the """"""""life history"""""""" of morphologically identified neurons. These studies are intended to examine the effects of ethanol upon intrinsic (cell cycle) and extrinsic (circadian rhythms) components of neurogenesis and gliogenesis. Cellular migration depends upon complex neuronal- glial interactions. The effects of ethanol on various factors controlling migration, e.g., the physical glial support, chemical cues such as glycoproteins and lectins in the extracellular matrix and cell adhesion molecules, and conduits for electrotonic communications, will be examined. Earlier studies have been shown that neuronal differentiation is affected by prenatal exposure to ethanol. The effects of prenatal exposure to ethanol on the arrival and synaptogenesis of monoaminergic and cholinergic """"""""non-specific"""""""" afferents, thalamic and callosal """"""""specific"""""""" afferents, and efferents in the pyramidal tract will be examined. The morpho-physiological nature of corticospinal neurons, the neurotransmitters of local circuit neurons, and the glucose utilization of projection neurons, local circuit neurons, and glia will be studied. These studies will examine the mechanisms, rather than the phenomenology of the teratological effects of ethanol. Knowledge of these mechanisms will provide insights to possible preventatives for FAS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA006916-06
Application #
3110349
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1985-07-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Osteopathy
DUNS #
City
Stratford
State
NJ
Country
United States
Zip Code
08084
Akinmboni, T O; Davis, N L; Falck, A J et al. (2018) Excipient exposure in very low birth weight preterm neonates. J Perinatol 38:169-174
Wellmann, Kristen A; George, Finney; Brnouti, Fares et al. (2015) Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure. Behav Brain Res 286:201-11
Bearer, Cynthia F; Wellmann, Kristen A; Tang, Ningfeng et al. (2015) Choline Ameliorates Deficits in Balance Caused by Acute Neonatal Ethanol Exposure. Cerebellum 14:413-20
Hicks, Steven D; Lewis, Lambert; Ritchie, Julie et al. (2012) Evaluation of cell proliferation, apoptosis, and DNA-repair genes as potential biomarkers for ethanol-induced CNS alterations. BMC Neurosci 13:128
(2012) Retraction statement. Paper by Michael W. Miller and Huaiyu Hu [Developmental Neuroscience 2009;31:50-57]. Dev Neurosci 33:548
Hicks, Steven D; Miller, Michael W (2011) Effects of ethanol on transforming growth factor ?1-dependent and -independent mechanisms of neural stem cell apoptosis. Exp Neurol 229:372-80
Mooney, S M; Miller, M W (2011) Role of neurotrophins on postnatal neurogenesis in the thalamus: prenatal exposure to ethanol. Neuroscience 179:256-66
Meszaros, Zsuzsa Szombathyne; Dimmock, Jacqueline A; Ploutz-Snyder, Robert et al. (2011) Accuracy of self-reported medical problems in patients with alcohol dependence and co-occurring schizophrenia or schizoaffective disorder. Schizophr Res 132:190-3
Mooney, Sandra M; Miller, Michael W (2010) Prenatal exposure to ethanol affects postnatal neurogenesis in thalamus. Exp Neurol 223:566-73
Lindke, Amanda L; Middleton, Frank A; Miller, Michael W (2010) Regulating the availability of transforming growth factor ß1 in B104 neuroblastoma cells. Exp Neurol 225:123-32

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