The extracellular fragment of GPNMB (Glycoprotein nonmelanosoma protein B, osteoactivin) improves memory and increases hippocampal GluA1 levels in mice

Kenta Murata, Yuta Yoshino, Kazuhiro Tsuruma, Shigeki Moriguchi, Atsushi Oyagi, Hirotaka Tanaka, Mitsue Ishisaka, Masamitsu Shimazawa, Kohji Fukunaga, Hideaki Hara

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Glycoprotein nonmelanoma protein B (GPNMB, alias osteoactivin), a type I transmembrane glycoprotein, is cleaved by extracellular proteases, resulting in release of an extracellular fragment (ECF). GPNMB is widely expressed by neurons within the CNS, including the hippocampus; however, its function in the brain remains unknown. Here, we investigated the role of GPNMB in memory and learning by using transgenic (Tg) mice over-expressing GPNMB (Tg mice on a BDF-1 background) and ECF-treated mice. In the hippocampus of both wild-type and Tg mice, GPNMB was highly expressed in neurons and astrocytes. Tg mice exhibited memory improvements in two types of learning tasks but were impaired in a passive-avoidance test. In Tg mice, the hippocampus displayed increased levels of the α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit GluA1. Intracerebroventricular administration of ECF (50 ng) to Institute of Cancer Research (ICR) mice also improved memory in a passive-avoidance test and increased hippocampal GluA1 levels 24 h after treatment. In Tg mice and ECF (0.25 μg/mL)-treated hippocampal slices, long-term potentiation was promoted. These findings suggest that GPNMB may be a novel target for research on higher order brain functions.

Original languageEnglish
Pages (from-to)583-594
Number of pages12
JournalJournal of Neurochemistry
Volume132
Issue number5
DOIs
Publication statusPublished - 2015 Mar 1

Keywords

  • AMPA receptor subunit GluA1
  • Glycoprotein nonmelanosoma protein B (GPNMB)
  • hippocampus
  • memory improvement
  • osteoactivin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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