In vivo hypoxia-induced neuronal damage in dentate gyrus of rat hippocampus: changes in NMDA receptors and the effect of MK-801.
Hypoxia is a major cause of ischaemia-induced neuronal damage. In the present study, we examined the effects of in vivo hypoxia on N-methyl-D-aspartate receptors (NMDAR) in the rat hippocampus. This model of in vivo hypoxia involved placing rats in a hypoxic chamber containing 5% O2 and 95% N2 for 30 min. In the hippocampus, neuronal cells in the CA3, the hilus of the dentate gyrus and the dentate gyrus (DG) were damaged. In the CA1, which is known to be vulnerable to ischaemic damage, neuronal cells did not show hypoxia-induced damage. In vivo hypoxia-induced damage caused morphological changes in neuronal cells, such as shrunken, spindle or triangular shapes accompanied by pyknotic nuclei, but did not induce the loss of neuronal cells. On the other hand, the number of binding sites for [3H]-1-[1-(2-thienyl)cyclohexyl]-3,4-piperidine hydrochloride (TCP) gradually decreased on and after 7 days, and then maximally decreased by 25% at 21 days after hypoxia. The number of NMDAR1-immunopositive cells was decreased by 22% in the DG, but was unchanged in the CA3. Furthermore, we examined the effect of a non-competitive NMDA antagonist, (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,b] cyclohepten-5,10-imine hydrogen maleate (MK-801), on against in vivo hypoxia. The administration of MK-801 (3 mg/kg, i.p.), 30 min before hypoxia treatment, partly protected against neuronal damage in the DG, but not in the CA3. These results suggest that hypoxia-induced neuronal damage in the DG involves, in part, the activation of NMDAR.
Matsuoka
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kitamura
Y
Y
Fukunaga
R
R
Shimohama
S
S
Nabeshima
T
T
Tooyama
I
I
Kimura
H
H
Taniguchi
T
T
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014316:Tritium
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine