Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress: Variation in Its Levels and Activity Distribution in Rat Hippocampus
Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress: Variation in Its Levels and Activity Distribution in Rat Hippocampus
复制标题
DOI：
10.1021/acschemneuro.7b00387
复制
发表时间：
2018-05-01
影响因子：
5
通讯作者：
Fiedler, Jenny L.
中科院分区：
文献类型：
--
作者：
Aguayo, Felipe I.;Pacheco, Anibal A.;Fiedler, Jenny L.
单一应激暴露通过重塑海马兴奋性突触的神经可塑性过程促进记忆形成，可能需要改变细胞外基质成分。我们验证了基质金属蛋白酶9 （MMP-9）在急性应激反应中改变其在大鼠海马中的活性和分布的假设。基质金属蛋白酶9 （MMP-9）是一种降解细胞外基质和突触蛋白组分的酶，如β -三磷酸甘聚糖（β - dg(43)）)。在抑制应激2.5 h后，我们发现(i)整个海马提取物中MMP-9水平和潜在活性增加，并伴有β - dg（43）裂解；（ii）海马辐射层和分子层等树突状区中MMP-9的免疫反应性显著增强。应激24 h后，我们发现(i)体细胞场，即锥体层和颗粒细胞层，突触场，主要是辐射层和海马分子层，MMP-9的净活性上升；（ii）海马突触eurosome部分富含MMP-9，但其潜在的酶活性没有变化，与剪切β - dg的恒定水平一致（43）。这些发现表明，应激触发了海马中MMP-9水平、净活性和亚细胞分布的特殊时序反应，表明其参与应激反应过程中底物的加工。
A single stress exposure facilitates memory formation through neuroplastic processes that reshape excitatory synapses in the hippocampus, probably requiring changes in extracellular matrix components. We tested the hypothesis that matrix metalloproteinase 9 (MMP-9), an enzyme that degrades components of extracellular matrix and synaptic proteins such as beta-dystroglycan (beta-DG(43)), changes their activity and distribution in rat hippocampus during the acute stress response. After 2.5 h of restraint stress, we found (i) increased MMP-9 levels and potential activity in whole hippocampal extracts, accompanied by beta-DG(43) cleavage, and (ii) a significant enhancement of MMP-9 immunoreactivity in dendritic fields such as stratum radiatum and the molecular layer of hippocampus. After 24 h of stress, we found that (i) MMP-9 net activity rises at somatic field, i.e., stratum pyramidale and granule cell layers, and also at synaptic field, mainly stratum radiatum and the molecular layer of hippocampus, and (ii) hippocampal synaptoneurosome fractions are enriched with MMP-9, without variation of its potential enzymatic activity, in accordance with the constant level of cleaved beta-DG(43). These findings indicate that stress triggers a peculiar timing response in the MMP-9 levels, net activity, and subcellular distribution in the hippocampus, suggesting its involvement in the processing of substrates during the stress response.