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Role of p75NTR in NMDAR-mediated excitotoxic brain injury in neonatal mice.
- Source :
-
Brain research [Brain Res] 2010 Oct 08; Vol. 1355, pp. 31-40. Date of Electronic Publication: 2010 Aug 06. - Publication Year :
- 2010
-
Abstract
- Background: Perinatal brain injury in preterm infants is a major cause of neurological handicap. The role of the neurotrophin receptor p75 (p75(NTR)) in the pathogenesis and repair of neonatal excitotoxic brain injury is unknown. Depending on a complex interplay of neurotrophin signalling, p75(NTR) can, in addition to its trophic function, also induce apoptosis.<br />Hypothesis: We hypothesised that excitotoxicity increases p75(NTR) expression and p75(NTR) knockout (KO) mice have a significantly smaller lesion size upon excitotoxicity as compared to wild-type (WT) mice.<br />Methods: We used an established animal model of neonatal excitotoxic brain injury mimicking several key aspects of human preterm brain damage. We subjected five-day-old WT and KO mice to excitotoxic injury by means of a single intracranial ibotenate injection (N-methyl-D-aspartate receptor agonist, NMDAR) into one brain hemisphere. Lesion size, number of activated caspase-3- and apoptosis-inducing factor (AIF)-positive cells were determined as outcome parameters. Gender analyses were taken into account retrospectively.<br />Results: NMDAR-mediated excitotoxicity induced an upregulation of p75(NTR) expression in the peri-lesion area. Lesion size was significantly increased in female KO as compared to male KO animals. Knockout of p75(NTR) reduced the number of activated caspase-3 but not AIF-positive cells after NMDAR-mediated excitotoxic injury independently of gender.<br />Conclusion: Since NMDAR-mediated excitotoxic brain injury induced p75(NTR) expression and caspase-3-activated apoptosis in p75(NTR) KO animals was decreased, we conclude that activation of p75(NTR) contributes to NMDAR-mediated apoptosis in the neonatal brain. An increase in lesion size in female animals after excitotoxic brain injury suggests that in females p75(NTR) seems to play a dual role.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Animals, Newborn
Apoptosis drug effects
Apoptosis physiology
Brain Injury, Chronic chemically induced
Brain Injury, Chronic pathology
Disease Models, Animal
Female
Male
Mice
Mice, Knockout
Receptors, N-Methyl-D-Aspartate drug effects
Receptors, Nerve Growth Factor genetics
Brain Injury, Chronic metabolism
Neurotoxins toxicity
Receptors, N-Methyl-D-Aspartate metabolism
Receptors, Nerve Growth Factor physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1355
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 20692240
- Full Text :
- https://doi.org/10.1016/j.brainres.2010.07.095