Regents' Professor and Chair |
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Research
Interests:
Our research addresses the question of whether the consumption of moderate amounts
of ethanol by mothers while they are pregnant causes long-term functional consequences
in the offspring's brain. Using a rat model of prenatal ethanol exposure, we
have observed that the consumption of moderate quantities of ethanol during
pregnancy can cause subtle but persistent neurochemical changes in the brain
of offspring. These changes occur in specific brain regions involved in the
consolidation of short term memory into long term memory, both in rats and in
humans. The neurochemical alterations caused by prenatal ethanol exposure decrease
activity-dependent enhancement of synaptic communication between neurons leading
to functional deficits in these brain regions. We believe that these changes
may contribute to the learning disabilities observed in children whose mothers
drank during pregnancy. The long-term goals of our research program are first,
to more clearly identify the specific neurochemical changes in the brain caused
by moderate drinking during pregnancy and then explore treatment strategies
that could compensate for these neurochemical changes with the hope that we
can overcome the learning disabilities resulting from prenatal ethanol exposure.
Selected Publications:
1. Sutherland,
R.J., McDonald, R.J. and Savage, D.D.: Prenatal exposure to moderate levels
of ethanol can have long-lasting effects on hippocampal synaptic plasticity
in adult offspring. Hippocampus
7:232-238, 1997.
2. Carpenter, S.P., Savage, D.D., Schultz, E.D. and Raucy, J.L.: Ethanol-mediated
transplacental induction of CYP2E1 in fetal rat liver. J.
Pharmacol. Exp. Ther.
282:1028-1036, 1997.
3. Allan, A.M., Weeber, E.J., Savage, D.D. and Caldwell, K.K.: Effect of prenatal
ethanol exposure on phospholipase C-?1 and phospholipase A2 in hippocampus and
medial frontal cortex of adult rat offspring. Alcoholism:
Clin. Exp. Res. 21:1534-1541,
1997.
4. Allan, A.M., Wu, H., Paxton, L.L., and Savage, D.D.: Prenatal ethanol exposure
alters modulation of the GABAA receptor-chloride channel complex in adult offspring.
J. Pharmacol. Exp. Ther. 284:250-257, 1998.
5. Perrone-Bizzozero, N.I., Isaacson, T.V., Keidan, G.M.O., Eriquat, C., Meiri,
K.F., Savage, D.D. and Allan, A.M.: Prenatal ethanol exposure decreases GAP-43
phosphorylation and Protein Kinase C activity in the hippocampus of adult rat
offspring. J.
Neurochem. 71:2104-2111, 1998.
6. Savage, D.D., Cruz, L.L., Duran, L.M. and Paxton, L.L.: Prenatal ethanol
exposure diminishes activity-dependent potentiation of amino acid neurotransmitter
release. Alcoholism:
Clin. Exp Res. 22:1771-1777, 1998.
7. Costa, E.T., Olivera, D.S., Meyer, D.A., Ferreira, V.M.M., Soto, E.E., Frausto,
S., Browning, M.D., Savage, D.D. and Valenzuela, C.F.: Fetal alcohol exposure
alters neurosteroid modulation of hippocampal NMDA receptors. J.
Biol. Chem.
275:38268-38274, 2000.
8. Weeber, E.J., Savage, D.D., Sutherland, R.J. and Caldwell, K.K.: Fear conditioning-induced
alterations in phospholipase C-?1a enzyme level and activity in rat hippocampal
formation and medial frontal cortex. Neurobiol
Learning and Memory 76:151-182,
2001.
9. Savage, D.D., Becher, M., de la Torre, A.J. and Sutherland, R.J.: Dose-dependent
effects of prenatal ethanol exposure on synaptic plasticity and learning in
mature offspring. Alcholism:
Clin. Exp. Res.
26:1752-1758, 2002.
10. Hamilton, D.A., Kodituwakku, P., Sutherland, R.J. and Savage, D.D.: Children
with Fetal Alcohol Syndrome are impaired at place learning but not cued-navigation
in a virtual Morris water task. Behavioral
Brain Research
143:85-94, 2003.
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