Relevance of Exocytotic Glutamate Release from Retinal Glia-猫眼课题宝

DOI：

10.1016/j.neuron.2012.03.027

发表时间：

2012-05

期刊：

Neuron

影响因子：

16.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

M. Slezak;A. Grosche;Aurore Niemiec;N. Tanimoto;T. Pannicke;T. Münch;Britni Crocker;P. Isope;W. Härtig;Susanne C Beck;G. Huber;G. Ferracci;M. Perraut;M. Reber;M. Miehe;V. Demais;C. Lévêque;D. Metzger;K. Szklarczyk;R. Przewłocki;M. Seeliger;Dominique Sage-Ciocca;J. Hirrlinger;A. Reichenbach;S. Reibel;F. Pfrieger

神经胶质细胞释放影响大脑发育、功能和疾病的分子。钙离子依赖的胞吐作用被认为是星形胶质细胞释放钙离子的潜在机制，但其在体内的生理意义仍存在争议。我们专注于神经胶质细胞胞吐作用对视网膜感觉转导的影响，为此，我们产生了转基因小鼠，通过Cre重组酶依赖性表达肉毒梭菌神经毒素血清型B轻链（切割囊泡相关膜蛋白1-3）来阻断胞吐作用。普遍存在的神经毒素表达导致围产期死亡和突触传递减少，从而验证转基因功能。Müller细胞中的毒素表达抑制囊泡谷氨酸释放并损害胶质细胞体积调节，但不影响视网膜组织学和视觉处理。我们的模型在体内研究胶质传递揭示了视网膜胶质细胞胞吐谷氨酸释放的特殊功能。

Glial cells release molecules that influence brain development, function, and disease. Calcium-dependent exocytosis has been proposed as potential release mechanism in astroglia, but the physiological relevance of "gliotransmission" in vivo remains controversial. We focused on the impact of glial exocytosis on sensory transduction in the retina. To this end, we generated transgenic mice to block exocytosis by Cre recombinase-dependent expression of the clostridial botulinum neurotoxin serotype B light chain, which cleaves vesicle-associated membrane protein 1-3. Ubiquitous and neuronal toxin expression caused perinatal lethality and a reduction of synaptic transmission thus validating transgene function. Toxin expression in Müller cells inhibited vesicular glutamate release and impaired glial volume regulation but left retinal histology and visual processing unaffected. Our model to study gliotransmission in vivo reveals specific functions of exocytotic glutamate release in retinal glia.

Relevance of Exocytotic Glutamate Release from Retinal Glia

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