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首页> 外文期刊>IBRO Reports >Interneurons secrete prosaposin, a neurotrophic factor, to attenuate kainic acid-induced neurotoxicity
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Interneurons secrete prosaposin, a neurotrophic factor, to attenuate kainic acid-induced neurotoxicity

机译：Interneurons分泌神经营养因子prosaposin，以减轻海藻酸诱导的神经毒性

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Highlights ? PS increased mainly in the axons of PV positive interneurons after kainic acid (KA) injection. ? Electron microscopy revealed PS containing vesicles in PV positive axons. ? PS is secreted with secretogranin from synapses. ? The increased PS in the interneurons was due to increases in PS+0, as in the choroid plexus. ? Interneurons produce and secrete intact PS around the hippocampal pyramidal neurons to protect them from KA neurotoxicity. Abstract Prosaposin (PS) is a secretory neurotrophic factor, as well as a regulator of lysosomal enzymes. We previously reported the up-regulation of PS and the possibility of its axonal transport by GABAergic interneurons after exocitotoxicity induced by kainic acid (KA), a glutamate analog. In the present study, we performed double immunostaining with PS and three calcium binding protein markers: parvalbumin (PV), calbindin, and calretinin, for the subpopulation of GABAergic interneurons, and clarified that the increased PS around the hippocampal pyramidal neurons after KA injection existed mainly in the axons of PV positive interneurons. Electron microscopy revealed PS containing vesicles in the PV positive axon. Double immunostaining with PS and secretogranin or synapsin suggested that PS is secreted with secretogranin from synapses. Based on the results from in situ hybridization with two alternative splicing forms of PS mRNA, the increase of PS in the interneurons was due to the increase of PS+0 (mRNA without 9-base insertion) as in the choroid plexus, but not PS+9 (mRNA with 9-base insertion). These results were similar to those from the choroid plexus, which secretes an intact form PS+0 to the cerebrospinal fluid. Neurons, especially PV positive GABAergic interneurons, produce and secrete the intact form of PS around hippocampal pyramidal neurons to protect them against KA neurotoxicity.
机译：强调 ？ PS的增加主要是在注射海藻酸（KA）后PV阳性中枢神经轴突。 ？电子显微镜显示PV阳性轴突中包含PS的囊泡。 ？ PS是由突触中的促分泌素分泌的。 ？中枢神经中PS的增加是由于脉络丛中PS + 0的增加。 ？中间神经元在海马锥体神经元周围产生并分泌完整的PS，以保护它们免受KA神经毒性。摘要Prosaposin（PS）是一种分泌性神经营养因子，也是溶酶体酶的调节剂。我们先前曾报道过谷氨酸类似物海藻酸（KA）诱发的外毒素中毒后，GABA能性中神经对PS的上调和轴突转运的可能性。在本研究中，我们对PS和三种钙结合蛋白标记物（parvalbumin（PV），calbindin和calretinin）进行了双重免疫染色，以检测GABA能神经元的亚群，并阐明在KA注射后，海马锥体神经元周围的PS增加主要在PV正中间神经元的轴突中。电子显微镜显示PV阳性轴突中包含PS的囊泡。 PS和促凝素或突触素的双重免疫染色提示PS是由突触分泌促凝素分泌的。根据与PS mRNA两种可变剪接形式原位杂交的结果，中间神经元中PS的增加是由于脉络丛中PS + 0（无9个碱基插入的mRNA）的增加，而不是PS +9（插入9个碱基的mRNA）。这些结果与脉络丛的结果相似，脉络丛将完整形式的PS + 0分泌到脑脊液中。神经元，特别是PV阳性的GABA能性中枢神经元，在海马锥体神经元周围产生并分泌完整形式的PS，以保护它们免受KA神经毒性。

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