In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 43 ( 2008-10-28), p. 16779-16784
Abstract:
White-matter damage is a leading cause of neurological handicap. Although hypoxia-ischemia and excitotoxicity are major pathogenic factors, a role for genetic influences was suggested recently. Thus, protracted gestational hypoxia was associated with white-matter damage (WMD) in rat pups but not in mouse pups. Indeed, microglial activation and vessel-wall density on postnatal days (P)1 and P10 were found increased in both mouse and rat pups, but cell death, astrogliosis, and myelination were only significantly altered in hypoxic rat pups. We investigated whether this species-related difference was ascribable to effects of antenatal hypoxia on the expression of glutamate receptor subunits by using immunocytochemistry, PCR, and excitotoxic double hit insult. Quantitative PCR in hypoxic mouse pups on P1 showed 2- to 4-fold down-regulation of the AMPA-receptor subunits -1, 2, and -4; of the kainate-receptor subunit GluR7; and of the metabotropic receptor subunits mGluR1, -2, -3, -5, and -7. None of the glutamate-receptor subunits was down-regulated in the hypoxic rat pups. NR2B was the only NMDA-receptor subunit that was down-regulated in hypoxic mice but not in hypoxic rat on P1. Ifenprodil administration to induce functional inhibition of NMDA containing NR2B-subunit receptors prevented hypoxia-induced myelination delay in rat pups. Intracerebral injection of a glutamate agonist produced a larger decrease in ibotenate-induced excitotoxic lesions in hypoxic mouse pups than in normoxic mouse pups. Gestational hypoxia may regulate the expression of specific glutamate-receptor subunits in fetal mice but not in fetal rats. Therefore, genetic factors may influence the susceptibility of rodents to WMD.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0803004105
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2008
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
Bookmarklink
