RGD Reference Report - Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus: A possible role of NMDAR mediated p75(NTR) upregulation. - Rat Genome Database

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Chronic hypobaric hypoxia induced apoptosis in CA1 region of hippocampus: A possible role of NMDAR mediated p75(NTR) upregulation.

Authors: Hota, SK  Barhwal, K  Singh, SB  Ilavazhagan, G 
Citation: Hota SK, etal., Exp Neurol. 2008 Feb 16;.
RGD ID: 2293315
Pubmed: PMID:18466900   (View Abstract at PubMed)
DOI: DOI:10.1016/j.expneurol.2008.01.030   (Journal Full-text)

Hypobaric hypoxia has been implicated with neural degeneration and memory loss. Though there has been considerable knowledge on the role of the p75(NTR) in triggering apoptosis, the occurrence of a similar mechanism in hypoxic stress still remains to be explored. We, in the present study, have tried to explore the role of p75(NTR) in mediating apoptosis in hypobaric hypoxia. Male Sprague Dawley rats were exposed to an altitude of 7,620 m for different durations. To study the contribution of apoptosis to hypobaric hypoxia induced cell death in the hippocampus, rat brains were examined for the occurrence of apoptosis by determining the number of cells showing DNA breaks using terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay and chromatin condensation using Hoechst staining along with estimation of caspase activity and expression of active Caspase 3. Expression of p75(NTR) was studied to determine its possible role in triggering apoptosis in hypobaric hypoxia. Exposure to hypobaric hypoxia was found to progressively increase the number of TUNEL positive and Hoechst positive cells along with increase in caspase activity, thus suggesting apoptotic mode of cell death. p75(NTR) was found to be upregulated on prolonged exposure to hypobaric hypoxia corresponding to the increase in the number of apoptotic cells. Further, reduced expression of p75(NTR) expression by antisense nucleotide administration significantly decreased apoptosis in the CA1 region of hippocampus. Blocking of NMDA receptors by MK801 interestingly decreased p75(NTR) expression and the number of TUNEL positive cells as compared to hypoxic animals. These findings suggest the regulation of p75(NTR) by NMDA receptors and its role in inducing apoptosis in hypoxia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypoxia  ISOCasp3 (Rattus norvegicus)2293315; 2293315 RGD 
Hypoxia  IEP 2293315 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to hypoxia  IEP 2293315 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)

Genes (Mus musculus)
Casp3  (caspase 3)

Genes (Homo sapiens)
CASP3  (caspase 3)


Additional Information