title: A prosaposin-derived Peptide alleviates kainic Acid-induced brain injury.
abstract: Four sphingolipid activator proteins (i.e., saposins A-D) are synthesized from a single precursor protein, prosaposin (PS), which exerts exogenous neurotrophic effects in vivo and in vitro. Kainic acid (KA) injection in rodents is a good model in which to study neurotrophic factor elevation; PS and its mRNA are increased in neurons and the choroid plexus in this animal model. An 18-mer peptide (LSELIINNATEELLIKGL; PS18) derived from the PS neurotrophic region prevents neuronal damage after ischemia, and PS18 is a potent candidate molecule for use in alleviating ischemia-induced learning disabilities and neuronal loss. KA is a glutamate analog that stimulates excitatory neurotransmitter release and induces ischemia-like neuronal degeneration; it has been used to define mechanisms involved in neurodegeneration and neuroprotection. In the present study, we demonstrate that a subcutaneous injection of 0.2 and 2.0 mg/kg PS18 significantly improved behavioral deficits of Wistar rats (n = 6 per group), and enhanced the survival of hippocampal and cortical neurons against neurotoxicity induced by 12 mg/kg KA compared with control animals. PS18 significantly protected hippocampal synapses against KA-induced destruction. To evaluate the extent of PS18- and KA-induced effects in these hippocampal regions, we performed histological evaluations using semithin sections stained with toluidine blue, as well as ordinal sections stained with hematoxylin and eosin. We revealed a distinctive feature of KA-induced brain injury, which reportedly mimics ischemia, but affects a much wider area than ischemia-induced injury: KA induced neuronal degeneration not only in the CA1 region, where neurons degenerate following ischemia, but also in the CA2, CA3, and CA4 hippocampal regions.
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: 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: 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: Ehime Prefectural University of Health Sciences, Iyo, Ehime, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Wakisaka
authors.affiliation: Department of Human Anatomy, Oita University Fuculty of Medicine, Yufu, Oita, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hamada
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: D000595:Amino Acid Sequence; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D049231:Saposins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000473:pathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C483347:Psap protein, rat; D049231:Saposins; D007608:Kainic Acid