The metabotropic glutamate receptor mGlu5 controls the onset of developmental apoptosis in cultured cerebellar neurons
The metabotropic glutamate receptor mGlu5 controls the onset of developmental apoptosis in cultured cerebellar neurons
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DOI：
10.1046/j.1460-9568.1998.00230.x
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发表时间：
1998-06-01
影响因子：
3.4
通讯作者：
Nicoletti, F
中科院分区：
文献类型：
--
作者：
Copani, A;Casabona, G;Nicoletti, F
在含10 mM K+的培养液中培养的小脑颗粒细胞在体外培养4-5天后发生凋亡，此时与多磷肌醇(PI)水解偶联的代谢性谷氨酸(MGlu)受体的活性开始下降。在4DIV的颗粒细胞中，mGlu受体亚型mGlu5高水平表达。另一种PI偶联的mGlu受体mGlu1a的表达在4DIV时很低，但在接下来的几天里表达增加。在4-5DIV的培养中，少数已经表现出凋亡表型的细胞缺乏mGlu5受体，但它们都表达mGlu1a受体。(I)mGlu5反义寡核苷酸，(Ii)mGlu受体拮抗剂，(+)-α-甲基-4-羧基苯甘氨酸，或(Iii)谷氨酸耗竭酶，丙氨酸氨基转移酶处理后，细胞的凋亡进程加快。相反，mGlu5受体的诱导过表达保护培养的颗粒细胞免受凋亡性死亡。我们认为，mGlu5受体的活性支持细胞存活，mGlu5受体表达的下降为原代培养的小脑颗粒细胞的程序性死亡提供了途径。
Cultured cerebellar granule cells grown in medium containing 10 mM K+ undergo apoptosis after 4-5 days in vitro (DIV), and, at that time, the activity of metabotropic glutamate (mGlu) receptors coupled to polyphosphoinositide (PI) hydrolysis begins to decline. In granule cells at 4 DIV, the mGlu receptor subtype mGlu5 was expressed at high levels. The expression of another PI-coupled mGlu receptor, the mGlu1a, was low at 4 DIV but increased during the following days. In cultures at 4-5 DIV, the few cells that already showed an apoptotic phenotype were devoid of mGlu5 receptors, but they all expressed mGlu1a receptors. The development of apoptosis was accelerated after treating the cultures with: (i) mGlu5 antisense oligonucleotides; (ii) the mixed mGlu receptor antagonist, (+)-alpha-methyl-4-carboxyphenylglycine; or (iii) the glutamate depleting enzyme, alanine aminotransferase. In contrast, an induced overexpression of mGlu5 receptors protected cultured granule cells against apoptotic death. We suggest that the activity of mGlu5 receptors supports cell survival, and a decline in the expression of mGlu5 receptors gives access to programmed cell death in cerebellar granule cells developing in primary cultures.