Reversal of Alcohol-Induced Learning Deficits in the Young Adult in a Model of Fetal Alcohol Syndrome
Reversal of Alcohol-Induced Learning Deficits in the Young Adult in a Model of Fetal Alcohol Syndrome
复制标题
在胎儿酒精综合症模型中逆转年轻人酒精引起的学习缺陷
作者：
M. Incerti;J. Vink;R. Roberson;L. Wood;D. Abebe;C. Spong
OBJECTIVE: To evaluate whether treatment with neuroprotective peptides to young adult mice prenatally exposed to alcohol reverses alcohol-induced learning deficits in a mouse model of fetal alcohol syndrome, whether the mechanism involves the N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid type A (GABAA) receptors, and whether it is related to glial cells. METHODS: C57Bl6/J mice were treated with alcohol (0.03 ml/g) or placebo on gestational day 8. On day 40, male mice exposed to alcohol in utero were treated daily for 10 days with D-NAPVSIPQ and D-SALLRSIPA (n=20) or placebo (n=13); and control offspring were treated with placebo (n=46), with the treatment blinded. Learning evaluation began after 3 days using the Morris watermaze and the T-maze. The hippocampus, cortex, and cerebellum were isolated. Expression of NR2A, NR2B, GABAAβ3, GABAAα5, vasoactive intestinal peptide (VIP), activity-dependent neuroprotective protein, and glial fibrillary acidic protein was measured using calibrator-normalized relative real-time polymerase chain reaction. Statistical analysis included analysis of variance and Fisher's protected least significant difference. RESULTS: Treatment with D-NAPVSIPQ and D-SALLRSIPA reversed the alcohol-induced learning deficit in both learning tests as well as the NR2A and NR2B down-regulation in the hippocampus and the up-regulation of NR2A in the cortex and NR2B in the cortex and cerebellum (all P<.05). No significant differences were found in GABAA expression. Moreover, the peptides changed activity-dependent neuroprotective protein expression in the cortex (P=.016) but not the down-regulation of VIP (P=.883), probably because the peptides are downstream from VIP. CONCLUSION: Alcohol-induced learning deficit was reversed and expression of NR2A and NR2B was restored in the hippocampus and cortex of young adult mice treated with D-NAPVSIPQ and D-SALLRSIPA. Given the role of NMDA receptors in learning, this may explain in part the mechanism of prevention of alcohol-induced learning deficits by D-NAPVSIPQ and D-SALLRSIPA.
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DOI：
--
发表时间：
2001
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
L. Beni‐Adani;I. Gozes;Y. Cohen;Y. Assaf;R. Steingart;D. Brenneman;O. Eizenberg;V. Trembolver;E. Shohami
通讯作者：
L. Beni‐Adani;I. Gozes;Y. Cohen;Y. Assaf;R. Steingart;D. Brenneman;O. Eizenberg;V. Trembolver;E. Shohami
DOI：
--
发表时间：
2001-05
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
C. Spong;D. Abebe;I. Gozes;D. Brenneman;Joannam . Hill
通讯作者：
C. Spong;D. Abebe;I. Gozes;D. Brenneman;Joannam . Hill
DOI：
--
发表时间：
1994-12
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Y. H. Lee;K. Spuhler-Phillips;P. Randall;S. W. Leslie
通讯作者：
Y. H. Lee;K. Spuhler-Phillips;P. Randall;S. W. Leslie
大鼠妊娠最后三分之一期间的产前乙醇暴露会降低 45 日龄后代的海马 NMDA 激动剂结合位点密度。
DOI：
10.1016/0741-8329(92)90007-w
发表时间：
1992
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Savage,DD;Queen,SA;Sanchez,CF;Paxton,LL;Mahoney,JC;Goodlett,CR;West,JR
通讯作者：
West,JR
影响因子：
56.9
作者：
Ikonomidou, C;Bittigau, P;Olney, JW
通讯作者：
Olney, JW