The PDGF B-chain is involved in the ontogenic susceptibility of the developing rat brain to NMDA toxicity

Tomoko Egawa-Tsuzuki, Masaki Ohno, Naoto Tanaka, Yoshihiro Takeuchi, Hidetaka Uramoto, Roland Faigle, Keiko Funa, Yoko Ishii, Masakiyo Sasahara

Research output: Contribution to journalArticle

Abstract

Hypoxic-ischemic (H-I) injury to neonatal brains can cause a life-long neuronal deficit because of increased susceptibility in the neonatal period. Excitotoxicity due to overstimulation of the N-methyl-D-aspartate receptor (NMDAR) is assumed to be the basis of the injury. However, the ontogenic profile of the susceptibility does not directly correlate with the levels of NMDAR expression. Platelet-derived growth factor B-chain (PDGF-B) has been reported to protect neurons by suppressing the NMDA-evoked current and translocating the glutamate transporter to the cell membrane. Thus, we assessed the relationship between the susceptibility to H-I injury and the expression of PDGF-B in neonatal rat brain. PDGF-B infusion before and after an intrastriatal NMDA injection significantly reduced the size of the lesions in 7-day-old rats, when they are most susceptible and the neuronal expression of PDGF-B is low. Fourteen-day-old neonatal rats were found to be resistant to NMDA injury, even though NMDARs are expressed at high levels in the brain at this age. Inhibition of PDGF-B protein synthesis by antisense oligodeoxynucleotides increased the size of the NMDA-induced lesions up to 6-fold at postnatal day 14, when PDGF-B is expressed at high levels in neurons. These data suggest that PDGF-B is an important physiological modulator of NMDAR excitability in the developing brain, and that the balance between the expression of NMDAR and PDGF-B partly determines the ontogenic susceptibility to brain injury. Enhancement of the PDGF-B/receptor signal pathway might rescue neonatal brains at risk of H-I injury.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalExperimental Neurology
Volume186
Issue number1
DOIs
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • Antisense oligonucleotides
  • Brain
  • Development
  • Excitotoxicity
  • Glutamate
  • Hypoxia
  • Immaturity
  • Ischemia
  • NMDA
  • Platelet-derived growth factor

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Egawa-Tsuzuki, T., Ohno, M., Tanaka, N., Takeuchi, Y., Uramoto, H., Faigle, R., Funa, K., Ishii, Y., & Sasahara, M. (2004). The PDGF B-chain is involved in the ontogenic susceptibility of the developing rat brain to NMDA toxicity. Experimental Neurology, 186(1), 89-98. https://doi.org/10.1016/j.expneurol.2003.11.001