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Prenatal Ethanol Exposure Decreases GAP‐43 Phosphorylation and Protein Kinase C Activity in the Hippocampus of Adult Rat Offspring
Author(s) -
PerroneBizzozero Nora I.,
Isaacson Tove V.,
Keidan Gregory M. O.,
Eriqat Cheryl,
Meiri Karina F.,
Savage Daniel D.,
Allan Andrea M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71052104.x
Subject(s) - offspring , long term potentiation , endocrinology , medicine , protein kinase c , phosphorylation , hippocampal formation , protein kinase a , kinase , hippocampus , biology , ethanol , fetus , western blot , biochemistry , pregnancy , receptor , genetics , gene
Consumption of moderate quantities of ethanol during pregnancy produces deficits in long‐term potentiation in the hippocampal formation of adult offspring. Protein kinase C (PKC)‐mediated phosphorylation of the presynaptic protein GAP‐43 is critical for the induction of long‐term potentiation. We tested the hypothesis that this system is affected in fetal alcohol‐exposed (FAE) rats by measuring GAP‐43 phosphorylation and PKC activity in the hippocampus of adult offspring of rat dams that had consumed one of three diets throughout gestation: (a) a 5% ethanol liquid diet, which produced a maternal blood ethanol concentration of 83 mg/dl (FAE); (b) an isocalorically equivalent 0% ethanol diet (pair‐fed); or (c) lab chow ad libitum. Western blot analysis using specific antibodies to PKC‐phosphorylated GAP‐43 revealed that FAE rats had an ∼50% reduction in the proportion of phosphorylated GAP‐43. Similarly, we found that PKC‐mediated incorporation of 32 P into GAP‐43 was reduced by 85% in hippocampal slices from FAE rats compared with both control groups. FAE animals also showed a 50% reduction in total hippocampal PKC activity, whereas the levels of six major PKC isozymes did not change in any of the diet groups. These results suggest that GAP‐43 phosphorylation deficits in rats prenatally exposed to moderate levels of ethanol are not due to alterations in the expression of either the enzyme or substrate protein, but rather to a defect in kinase activation.