The expression of glial cell line-derived neurotrophic factor mRNA by antidepressants involves matrix metalloproteinase-9 activation in rat astroglial cells
The expression of glial cell line-derived neurotrophic factor mRNA by antidepressants involves matrix metalloproteinase-9 activation in rat astroglial cells
复制标题
DOI：
10.1016/j.bbrc.2016.09.070
复制
发表时间：
2016-10-28
影响因子：
3.1
通讯作者：
Takebayashi, Minoru
中科院分区：
文献类型：
--
作者：
Abe, Hiromi;Hisaoka-Nakashima, Kazue;Takebayashi, Minoru
神经营养/生长因子来源于神经胶质细胞，特别是星形胶质细胞，有牵连的情绪障碍和抗抑郁药物的药理作用。以往的研究表明，胶质细胞源性神经营养因子（GDNF）的释放诱导的三环类抗抑郁药阿米替林显着抑制大鼠C6星形胶质细胞（C6细胞）的广谱基质金属蛋白酶（MMP）抑制剂。然而，阿米替林是否影响MMP酶活性或表达尚不清楚，MMP亚型尚未确定。本研究采用明胶酶谱法（一种体外酶活性测定法）在C6细胞和原代培养的大鼠星形胶质细胞（原代星形胶质细胞）中测定抗抑郁药对MMP活性的影响。阿米替林处理增加MMP-9酶谱活性，而不改变MMP-9 mRNA的表达在C6细胞。几种不同类型的抗抑郁药显着增加酶谱MMP-9的活性在C6细胞和初级星形胶质细胞，而抗精神病药物没有抗抑郁药的药理活性没有。选择性抑制MMP-9可完全阻断阿米替林诱导的C6细胞GDNF mRNA表达。用外源性重组MMP-9处理C6细胞和原代星形胶质细胞增加GDNF mRNA表达，与阿米替林观察到的结果相似。抑制MMP-3阻断阿米替林诱导的MMP-9在C6细胞和原代星形胶质细胞中的酶谱激活，表明MMP-3是MMP-9活性所必需的。目前的研究表明，MMP-9的激活是必不可少的阿米替林诱导的GDNF mRNA在星形胶质细胞的表达，并进一步支持星形胶质细胞神经营养生长因子的作用，抗抑郁药的药理作用。(C)2016 Elsevier Inc. All rights reserved.
Neurotrophic/growth factors derived from glial cells, especially astrocytes, have been implicated in mood disorders and the pharmacological effects of antidepressant drugs. Previous studies demonstrated that the release of glial cell line-derived neurotrophic factor (GDNF) induced by the tricyclic antidepressant amitriptyline was significantly inhibited by a broad-spectrum matrix metalloproteinase (MMP) inhibitor in rat C6 astroglial cells (C6 cells). However, it is unknown whether amitriptyline affects MMP enzymatic activity or expression, and the MMP subtype has yet to be identified. The current study measured the effect of antidepressants on MMP activity with gelatin zymography, an in vitro assay for enzymatic activity, in C6 cells and primary cultured rat astrocytes (primary astrocytes). Treatment with amitriptyline increased zymographic MMP-9 activity without changing MMP-9 mRNA expression in C6 cells. Several different classes of antidepressants significantly increased zymographic MMP-9 activity in C6 cells and primary astrocytes, whereas antipsychotic drugs without antidepressant pharmacological activity did not. The amitriptyline-induced expression of GDNF mRNA was completely blocked by selective inhibition of MMP-9 in C6 cells. Treatment of C6 cells and primary astrocytes with exogenous recombinant MMP-9 increased GDNF mRNA expression, similar to that observed with amitriptyline. Inhibiting MMP-3 blocked amitriptyline-induced zymographic MMP-9 activation in C6 cells and primary astrocytes, indicating that MMP-3 is necessary for MMP-9 activity. The current study suggests that MMP-9 activation is indispensable in the amitriptyline-induced expression of GDNF mRNA in astrocytes and further supports a role of astrocytic neurotrophicigrowth factors in the pharmacological effect of antidepressants. (C) 2016 Elsevier Inc. All rights reserved.