Antidepressant treatments regulate matrix metalloproteinases-2 and -9 (MMP-2/MMP-9) and tissue inhibitors of the metalloproteinases (TIMPs 1-4) in the adult rat hippocampus
Antidepressant treatments regulate matrix metalloproteinases-2 and -9 (MMP-2/MMP-9) and tissue inhibitors of the metalloproteinases (TIMPs 1-4) in the adult rat hippocampus
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DOI：
10.1002/syn.20529
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发表时间：
2008-08-01
期刊：
影响因子：
2.3
通讯作者：
Vaidya, Vidita A.
中科院分区：
文献类型：
--
作者：
Benekareddy, Madhurima;Mehrotra, Purvi;Vaidya, Vidita A.
抗抑郁药诱导成人海马区的结构重建，包括树突树枝、轴突萌发、神经发生和内皮细胞增殖的变化。这种形式的结构可塑性发生在细胞外基质环境的背景下，并已知受基质金属蛋白酶(MMPs)，特别是基质金属蛋白酶-2/9及其内源性调节因子--金属蛋白酶组织抑制因子(TIMPs 1-4)的调节。考虑到抗抑郁药物治疗引起的海马区结构重建，我们推测抗抑郁药物可能调节基质金属蛋白酶-2/9和基质金属蛋白酶1-4的表达和活性。用放射原位杂交法检测不同种类的抗抑郁药，即电惊厥发作、氟西汀、三羟环丙胺和地昔帕明对大鼠海马区基质金属蛋白酶-2、基质金属蛋白酶-9和基质金属蛋白酶组织抑制因子1-4基因表达的影响。此外，酶谱研究解决了急性和慢性服用抗抑郁药后对基质金属蛋白酶-2/9明胶酶活性的调节。我们观察到，急性和慢性ECS不同地调节了海马区MMP2/9和TIMPs1-4的转录水平，并增加了明胶酶的活性。另一方面，急性和慢性药物抗抑郁药不同地改变TIMPs的表达，而对海马区没有任何观察到的影响。MMP2/9的表达或活性。这些发现增加了细胞外基质修饰酶及其内源性调节因子作为抗抑郁药物治疗靶点的可能性，并表明它们可能有助于抗抑郁药物介导的海马体结构可塑性。
Antidepressants induce structural remodeling in the adult hippocampus, including changes in dendritic arbors, axonal sprouting, neurogenesis, and endothelial cell proliferation. Such forms of structural plasticity take place in the context of the extracellular matrix environment and are known to be regulated by matrix metalloproteinases (MMPs), in particular MMP-2/9, and their endogenous regulators, the tissue inhibitors of the metalloproteinases (TIMPs 1-4). Given the hippocampal structural remodeling associated with antidepressant treatments, we hypothesized that antidepressants may regulate the expression and activity of MMP-2/9 and TIMPs 1-4. The influence of distinct classes of antidepressants, namely, electroconvulsive seizure, fluoxetine, tranylcypromine, and desipramine, on the gene expression of MMP-2, MMP-9, and TIMPs 1-4 in the hippocampus was determined using radioactive in situ hybridization. In addition, zymography studies addressed the regulation of the gelatinase activity of MMP-2/9 following acute and chronic antidepressant administration. We observed that acute and chronic ECS differentially regulate the transcript levels of MMP-2/9 and TIMPs 1-4 and also increase gelatinase activity in the hippocampus. Acute and chronic pharmacological antidepressants on the other hand differentially alter the expression of the TIMPs without any observed effect on hippocampal. MMP2/9 expression or activity. These findings raise the possibility that extracellular matrix modifying enzymes and their endogenous regulators may serve as targets for antidepressant treatments and suggests the possibility that they may contribute to antidepressant-mediated structural plasticity in the hippocampus.