Serotonin depletion exacerbates changes in striatal gene expression following quinolinic acid injection

被引:13
作者
Cummings, TJ
Walker, PD
机构
[1] WAYNE STATE UNIV,DEPT ANAT & CELL BIOL,SCH MED,DETROIT,MI 48201
[2] WAYNE STATE UNIV,CELLULAR & CLIN NEUROBIOL PROGRAM,SCH MED,DEPT PSYCHIAT & BEHAV SCI,DETROIT,MI 48201
[3] WAYNE STATE UNIV,DEPT NEUROL SURG,SCH MED,DETROIT,MI 48201
关键词
preprotachykinin; preproenkephalin; Zif/268; pCPA; N-methyl-D-aspartate receptor; basal ganglia;
D O I
10.1016/S0006-8993(96)01053-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Controversy exists as to whether serotonin (5-HT) plays a neuroprotective role during brain injury, We sought to determine if prior 5-HT depletion alters gene expression patterns normally associated with NMDA receptor-mediated excitotoxicity of the rodent striatum. Adult male Sprague-Dawley rats were treated systemically with saline or p-chlorophenylalanine (pCPA, 350 mg/kg) to block 5-HT synthesis. After 3 days, these rats received unilateral injection (1 mu l) of quinolinic acid (QA, 40 mu g in 0.1 M phosphate buffered saline, pH 7.4) or saline vehicle directly into the anterior striatum. All rats were sacrificed 6 or 48 h later. Striatal tissues containing the saline or QA injection site were subjected to Northern analysis of preprotachykinin (PPT), preproenkephalin (PPE), and zif/268 mRNAs, as well as HPLC-EC detection of monoamines. At the time of the intrastriatal injection, 5-HT levels were depleted greater than 95% by pCPA as compared to saline controls. At 48 h post-QA injection, PPT and PPE mRNAs were markedly reduced within the striatal lesion site of saline/QA and pCPA/QA groups with respect to their contralateral uninjected control sides. In the pCPA/QA group, striatal PPE and PPT mRNA levels were further reduced as compared to the saline/QA group with PPE mRNA reductions reaching statistical significance at 95% (ANOVA with Scheffe F-test). Exacerbation of the excitotoxic lesion in the 5-HT depleted rat was further exemplified by a larger increase in zif/268 mRNA measured at 6 h post-intrastriatal injection in the pCPA/QA group as compared to saline/QA animals (P < 0.05 by ANOVA with Scheffe F-test). These results suggest that 5-HT depletion may adversely affect neuronal survival following intrastriatal QA exposure and lend support to the hypothesis that increasing 5-HT levels during NMDA receptor-mediated excitotoxicity may spare neurons destined to degenerate.
引用
收藏
页码:240 / 248
页数:9
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