Temporal changes in prosaposin expression in the rat dentate gyrus after birth

PLoS One. 2014 May 28;9(5):e95883. doi: 10.1371/journal.pone.0095883. eCollection 2014.

Abstract

Neurogenesis in the hippocampal dentate gyrus occurs constitutively throughout postnatal life. Adult neurogenesis includes a multistep process that ends with the formation of a postmitotic and functionally integrated new neuron. During adult neurogenesis, various markers are expressed, including GFAP, nestin, Pax6, polysialic acid-neural cell adhesion molecule (PSA-NCAM), neuronal nuclei (NeuN), doublecortin, TUC-4, Tuj-1, and calretinin. Prosaposin is the precursor of saposins A-D; it is found in various organs and can be excreted. Strong prosaposin expression has been demonstrated in the developing brain including the hippocampus, and its neurotrophic activity has been proposed. This study investigated changes in prosaposin in the dentate gyrus of young and adult rats using double immunohistochemistry with antibodies to prosaposin, PSA-NCAM, and NeuN. Prosaposin immunoreactivity was intense in the dentate gyrus at postnatal day 3 (P3) and P7, but decreased gradually after P14. In the dentate gyrus at P28, immature PSA-NCAM-positive neurons localized exclusively in the subgranular zone were prosaposin-negative, whereas mature Neu-N-positive neurons were positive for prosaposin. Furthermore, these prosaposin-negative immature neurons were saposin B-positive, suggesting that the neurons take up and degrade prosaposin. In situ hybridization assays showed that prosaposin in the adult dentate gyrus is dominantly the Pro+9 type, a secreted type of prosaposin. These results imply that prosaposin secreted from mature neurons stimulates proliferation and maturation of immature neurons in the dentate gyrus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Dentate Gyrus / growth & development
  • Dentate Gyrus / metabolism*
  • Doublecortin Protein
  • Gene Expression Regulation, Developmental / physiology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Microscopy, Confocal
  • Neurogenesis / physiology*
  • Oligonucleotide Probes / genetics
  • Rats
  • Saposins / metabolism*

Substances

  • Dcx protein, rat
  • Doublecortin Protein
  • Oligonucleotide Probes
  • Psap protein, rat
  • Saposins

Grants and funding

This study was supported in part by grants to TS (No. 25450466), NK (No. 24590254), and SM (No. 25462295), from the Ministry of Education, Culture, Sports, Science and Technology, of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.