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UC Davis Health System

Prenatal alcohol exposure found to affect key developmental brain proteins

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Prenatal alcohol exposure may be particularly destructive for neurotrophins, a family of peptides that influence the growth, development and functional plasticity of the fetal brain. A new rodent study of alcohol's effects on three key neurotrophins has found that, even though environmental enrichment may be able to improve some fetal-alcohol effects, those benefits do not appear to be mediated by neurotrophins.

Results are published in the October issue of Alcoholism: Clinical & Experimental Research.

"Neurotrophins are produced in the nervous system and are critical for normal development of the brain," explained Robert F. Berman, a professor in the Department of Neurological Surgery and at the Center for Neuroscience at the University of California, Davis, as well as corresponding author for the study.

"Neurotrophins also play important roles in learning and memory, and contribute to the repair of the brain following injury or stress. We chose to examine three — nerve growth factor (NGF), neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) — because previous research had shown that prenatal alcohol exposure alters their levels in the brain, and that treatment of other types of brain injury with NGF or BDNF can be beneficial."

Researchers divided 22 pregnant Sprague-Dawley rats into four groups: Zero (receiving 0 g of alcohol), Low (4 g/kg/day), High (6 g/kg/day) and Naïve (untreated pregnant rats). The two alcohol groups were given alcohol on gestational days eight to 20. After weaning on postnatal day 21, the 228 offspring were housed for six weeks in one of three conditions: Isolated, Social or Enriched. Levels of NGF, NT-3 and BDNF were then measured in the offsprings' frontal cortex, occipital cortex, hippocampus and cerebellar vermis.

Robert Berman"While the importance of the postnatal rearing environment for brain development is clear, we need additional research to aid in devising rational treatment strategies for fetal alcohol spectrum disorders, including fetal alcohol syndrome."
— Robert Berman, professor of neurological surgery

"We found that prenatal alcohol exposure generally increased brain neurotrophin levels in adult rats," said Berman. "This suggests that neurotrophin levels increased as compensation for damage to the developing brain from prenatal alcohol exposure. Results also demonstrated that the effects of prenatal alcohol exposure can be enduring and last into adulthood."

Previous rodent research conducted by Berman had shown that rearing rats in an enriched environment following prenatal alcohol exposure improved their motor function as well as learning and memory.

"In this study, we found that being raised in an enriched environment, with ample opportunities for motor and sensory stimulation and social interactions, unexpectedly resulted in reduced levels of neurotrophins in some areas of the cortex, but not in other areas that are well known to be affected by prenatal alcohol exposure," Berman said.

When both sets of findings are considered together, Berman added, they indicate that the effects of prenatal alcohol exposure and environmental rearing conditions on neurotrophin levels are largely independent, with little evidence that one directly influenced the other's effects on neurotrophin levels.

"In other words," said Berman, "our results did not support our hypothesis that the beneficial effects of early environmental enrichment in rats exposed prenatally to alcohol were mediated directly by the three neurotrophins we examined in four specific brain areas."

This means that the molecular and cellular mechanisms underlying environmental enrichment effects after prenatal alcohol exposure are still not understood, said Berman.

"While the importance of the postnatal rearing environment for brain development is clear, we need additional research to aid in devising rational treatment strategies for fetal alcohol spectrum disorders, including fetal alcohol syndrome," Berman said.

ACER

Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Environmental Enrichment Alters Neurotrophin Levels after Fetal Alcohol Exposure in Rats," were: Elizabeth A. Parks of the Neuroscience Program and Department of Neurological Surgery at the University of California, Davis; and Andrew P. McMechan and John H. Hannigan of the Department of Obstetrics and Gynecology and the C.S. Mott Center for Human Growth and Development in the School of Medicine and the Department of Psychology at Wayne State University. The study was funded by the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism.

Journalists: A full copy of the manuscript may be obtained by contacting Mary Newcomb with the ACER Editorial Office at (317) 375-0819, e-mail mnewcomb-acer@earthlink.net, or by visiting http://www.blackwell-synergy.com/loi/acer.

UC Davis Health System is an academic medical center that includes a top-ranked school of medicine, a 577-bed acute care hospital, the proposed Betty Irene Moore School of Nursing, a National Cancer Institute-designated cancer center, the unique M.I.N.D. Institute for the study of neurodevelopmental disorders, a comprehensive children's hospital, a level 1 trauma center and outpatient clinics in communities throughout the Sacramento region. Consistently ranked among the nation's top medical schools and best hospitals, UC Davis has established itself as a national leader in telehealth, rural medicine, cancer, neurodevelopmental disorders, vascular medicine, and trauma and emergency medicine. Other areas of research strength include clinical and translational science, regenerative medicine, infectious disease, neuroscience, functional genomics and mouse biology, comparative medicine and nutrition, among many others.