Fetal alcohol exposure alters GAP-43 phosphorylation and protein kinase C responses to contextual fear conditioning in the hippocampus of adult rat offspring.
Fetal alcohol exposure alters GAP-43 phosphorylation and protein kinase C responses to contextual fear conditioning in the hippocampus of adult rat offspring.
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胎儿酒精暴露会改变成年大鼠后代海马体中 GAP-43 磷酸化和蛋白激酶 C 对情境恐惧调节的反应。
DOI：
10.1097/01.alc.0000106308.50817.b3
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Perrone-Bizzozero,NoraI
中科院分区：
文献类型：
--
作者：
Tanner,DanielC;Githinji,AnnW;Young,ElizabethA;Meiri,Karina;Savage,DanielD;Perrone-Bizzozero,NoraI
Abstract:Background:The growth‐ and plasticity‐associated protein GAP‐43 plays a significant role in the establishment and remodeling of neuronal connections. We have previously shown that GAP‐43 levels, protein kinase C (PKC) activity, and GAP‐43 phosphorylation increase during contextual fear conditioning and that fetal alcohol exposure (FAE) decreases PKC activity and GAP‐43 phosphorylation in the hippocampus of adult offspring. Drawing on these observations, we hypothesized that FAE manifests its cognitive impairment by disrupting PKC activation and membrane translocation, thereby decreasing GAP‐43 phosphorylation and function.Methods:Three groups of pregnant rat dams (FAE and two control diet groups) were placed on different diet regimens. Offspring from each of these groups were placed into each of four test groups, a contextual fear conditioned (CFC) group, a naïve unhandled group, and two nonlearning stress control groups. Hippocampi were dissected, homogenized, and used to prepare a cytosolic and a membrane fraction. These fractions were probed for total GAP‐43, PKC‐phosphorylated GAP‐43, and several PKC subtypes. PKC activity also was measured in total homogenates.Results:Compared with both control diet groups, FAE animals showed a deficit in the activation of PKC in the hippocampus at 24 hr but not at 1.5 hr after CFC. Likewise, we found that the amount of GAP‐43 and its phosphorylation were decreased 24 hr after CFC in FAE rats but not at early times after training. Analysis of the translocation of various PKC isoforms revealed that FAE animals had decreased levels of membrane‐bound PKC β2and PKC ε 24 hr after CFC.Conclusions:Considering the role of PKC activation and GAP‐43 phosphorylation in synaptic plasticity, our results suggest that deficient translocation of PKC β2and PKC ε in the hippocampus may mediate the electrophysiological and behavioral deficits observed in fetal alcohol exposed animals.
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DOI：
--
发表时间：
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期刊：
Psychobiology
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DOI：
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Alcoholism, clinical and experimental research.
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DOI：
10.1016/0741-8329(92)90007-w
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1992
期刊：
Alcohol (Fayetteville, N.Y.)
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作者：
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DOI：
10.1001/jama.1991.03460150065025
发表时间：
1991-04
影响因子：
3.8
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通讯作者：
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