N-methyl-D-aspartate receptors mediate activation of the c-fos proto-oncogene in a model of brain injury.
The proto-oncogene c-fos is rapidly and transiently induced in the CNS by a variety of stimuli. Brain injury, disruption of pia-arachnoid in a limited area, is one of the situations that leads to a dramatic increase in c-fos immunoreactivity. This increase is limited to the lesioned hemisphere. Injections of atropine (25 mg/kg, i.p.), naltrexone (5 mg/kg, i.p.), nifedipine (5 mg/kg, i.p.), and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (20 mg/kg, i.p.), prior to the injury, did not affect the activation of c-fos as assessed by immunohistochemistry in adult Sprague-Dawley rats perfused 2 h after the lesion. The non-competitive N-methyl-D-aspartate antagonists ketamine (100 mg/kg, i.p.) and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] (1 and 3 mg/kg, i.p.) markedly reduced c-fos activation. Phencyclidine (10 mg/kg, i.p.) produced a slight reduction in damage-induced fos activation. This study suggests that c-fos activation in this particular model is N-methyl-D-aspartate receptor-mediated and supports the idea that the fos proto-oncogene might play a role in plasticity and/or neurotoxic changes following brain damage.
Herrera
D G
DG
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Robertson
H A
HA
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D000927:Anticonvulsants; D004268:DNA-Binding Proteins; D003986:Dibenzocycloheptenes; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D016291:Dizocilpine Maleate; D001285:Atropine; D009543:Nifedipine; D010622:Phencyclidine