The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury

James W. Sharp, Stephen M. Sagar, Kinya Hisanaga, Pat Jasper, Frank R Sharp

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions-except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.

Original languageEnglish (US)
Pages (from-to)323-332
Number of pages10
JournalExperimental Neurology
Volume109
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

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Proto-Oncogene Proteins c-fos
N-Methyl-D-Aspartate Receptors
Wounds and Injuries
Intraventricular Injections
Quisqualic Acid
Quinolinic Acid
Neurons
Excitatory Amino Acids
Proteins
Nuclear Proteins
In Situ Hybridization
Glutamic Acid
Hippocampus
Monoclonal Antibodies
Gene Expression
Messenger RNA
Injections
Antibodies
Brain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neurology

Cite this

The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury. / Sharp, James W.; Sagar, Stephen M.; Hisanaga, Kinya; Jasper, Pat; Sharp, Frank R.

In: Experimental Neurology, Vol. 109, No. 3, 1990, p. 323-332.

Research output: Contribution to journalArticle

Sharp, James W. ; Sagar, Stephen M. ; Hisanaga, Kinya ; Jasper, Pat ; Sharp, Frank R. / The NMDA receptor mediates cortical induction of fos and fos-related antigens following cortical injury. In: Experimental Neurology. 1990 ; Vol. 109, No. 3. pp. 323-332.
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