Acta Neuropathologica

, Volume 109, Issue 5, pp 475–482 | Cite as

Cytomegalovirus infection inhibits the expression of N-methyl-d-aspartate receptors in the developing mouse hippocampus and primary neuronal cultures

  • Isao Kosugi
  • Hideya Kawasaki
  • Takashi Tsuchida
  • Yoshihiro Tsutsui
Regular Paper

Abstract

Cytomegalovirus (CMV) is the most significant infectious cause of developmental brain disorders in humans. The infection occasionally persists and causes neurological disorders. The N-methyl-d-aspartate (NMDA) subtype of glutamate receptors is essential for the development and plasticity of synapses, but also is involved in neuronal excitotoxicity during viral infection. Here we investigated the effects of murine CMV (MCMV) infection on the expression of NMDA receptors in the hippocampal neurons of neonatal mice and primary neuronal cultures. Viral antigen was mostly found in hippocampal pyramidal neurons from the CA1 to CA3. Image analysis of immunohistochemistry demonstrated that the expression of NMDA receptor subunit 1 (NMDA-R1) protein in CA1 neurons of MCMV-infected brain was reduced to 40% of that in uninfected brain. The signal of in situ hybridization for NMDA-R1 mRNA was also decreased in CA1 neurons of MCMV-infected brain. In primary neuronal cultures, reduction of NMDA-R1 expression in MCMV-infected neurons was also detected by immunocytochemistry and Western blotting. These results suggest that reduction of NMDA receptor expression by MCMV infection may cause a decrease in the susceptibility of the neurons to excitotoxic cell death, and may be related to the establishment of viral persistence and functional disturbances in MCMV-infected neurons.

Keywords

Cytomegalovirus NMDA receptor Cerebral neuron Neuronal excitotoxicity Development 

Notes

Acknowledgement

This work was supported in part by a grant (no. 15390126) from the Ministry of Education, Science, Culture and Technology, Japan.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Isao Kosugi
    • 1
  • Hideya Kawasaki
    • 1
  • Takashi Tsuchida
    • 1
  • Yoshihiro Tsutsui
    • 1
  1. 1.Department of PathologyHamamatsu University School of MedicineHamamatsuJapan

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