title: Prosaposin overexpression following kainic acid-induced neurotoxicity.
abstract: Because excessive glutamate release is believed to play a pivotal role in numerous neuropathological disorders, such as ischemia or seizure, we aimed to investigate whether intrinsic prosaposin (PS), a neuroprotective factor when supplied exogenously in vivo or in vitro, is up-regulated after the excitotoxicity induced by kainic acid (KA), a glutamate analog. In the present study, PS immunoreactivity and its mRNA expression in the hippocampal and cortical neurons showed significant increases on day 3 after KA injection, and high PS levels were maintained even after 3 weeks. The increase in PS, but not saposins, detected by immunoblot analysis suggests that the increase in PS-like immunoreactivity after KA injection was not due to an increase in saposins as lysosomal enzymes after neuronal damage, but rather to an increase in PS as a neurotrophic factor to improve neuronal survival. Furthermore, several neurons with slender nuclei inside/outside of the pyramidal layer showed more intense PS mRNA expression than other pyramidal neurons. Based on the results from double immunostaining using anti-PS and anti-GABA antibodies, these neurons were shown to be GABAergic interneurons in the extra- and intra-pyramidal layers. In the cerebral cortex, several large neurons in the V layer showed very intense PS mRNA expression 3 days after KA injection. The choroid plexus showed intense PS mRNA expression even in the normal rat, and the intensity increased significantly after KA injection. The present study indicates that inhibitory interneurons as well as stimulated hippocampal pyramidal and cortical neurons synthesize PS for neuronal survival, and the choroid plexus is highly activated to synthesize PS, which may prevent neurons from excitotoxic neuronal damage. To the best of our knowledge, this is the first study that demonstrates axonal transport and increased production of neurotrophic factor PS after KA injection.
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nabeka
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Uematsu
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Takechi
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimokawa
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yamamiya
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Doihara
authors.affiliation: Laboratory of Veterinary Anatomy, Faculty of Applied Biological Sciences, Gifu University, Yanagido, Gifu, Japan.
authors.forename: Shouichiro
authors.initials: S
authors.lastname: Saito
authors.affiliation: Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D002831:Choroid Plexus / Q000187:drug effects; D059330:GABAergic Neurons / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D017403:In Situ Hybridization; D007395:Interneurons / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes; D051381:Rats; D017208:Rats, Wistar; D049231:Saposins / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
chemical_list: C483345:PSAP protein, human; D049231:Saposins; D005680:gamma-Aminobutyric Acid; D007608:Kainic Acid