Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5736422 | IBRO Reports | 2017 | 16 Pages |
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 PSÂ +Â 0 (mRNA without 9-base insertion) as in the choroid plexus, but not PSÂ +Â 9 (mRNA with 9-base insertion). These results were similar to those from the choroid plexus, which secretes an intact form PSÂ +Â 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.
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Authors
Hiroaki Nabeka, Shouichiro Saito, Xuan Li, Tetsuya Shimokawa, Md. Sakirul Islam Khan, Kimiko Yamamiya, Soichiro Kawabe, Takuya Doihara, Fumihiko Hamada, Naoto Kobayashi, Seiji Matsuda,