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Endocrine Abstracts (2016) 44 P141 | DOI: 10.1530/endoabs.44.P141

SFEBES2016 Poster Presentations Neuroendocrinology and pituitary (34 abstracts)

Hypobaric hypoxia-induced neurodegeneration and memory impairment is glucocorticoid receptor dependent

Iswar Baitharu 1, , Satya Narayan Deep 1 & Govindasamy Ilavazhagan 1,


1Defense Institute of Physiology and Allied Sciences, New Delhi, Delhi, India; 2Sambalpur University, Sambalpur, Odisha, India;
3Hindustan University, Chennai, Tamilnadu, India.


Chronic exposure to hypobaric hypoxia (HH) causes neurodegeneration and loss of memory. The underlying mechanisms of HH-induced memory impairment have been attributed to prolonged elevated corticosterone level in hippocampus leading to augmented glutamate excitotoxicity, oxidative stress, alteration of neurotransmitter level or their receptors and calcium mediated signaling. Whether this corticosterone mediated neurodegenerative effect occurs through overstimulation of glucocorticoid receptors (GRs) or is independent of the GRs, is not known. Four groups of rats were taken and GR blocker mifepristone was administered intraperitoneally during exposure to HH from 3rd to 7th days. Our results showed duration dependent transcriptional upregulation of GRs and MRs following exposure to HH. Prolonged exposure to HH for 7 days augmented the translocation of GRs from cytosol to nucleus. Inhibition of GRs during hypoxic exposure improved the hippocampal ATP level and modulated the apoptotic markers like p53, Bcl2 and Bax. Decreased expression of L-type calcium channel and NR1 subunit of NMDA receptors were also observed following administration of mifepristone during hypoxic exposure. Morphological studies following mifepristone administration during hypoxic exposure showed decreased number of pyknotic cells in hippocampus and decrease in apoptotic and necrotic cells in the CA3 region of hippocampus. The study indicates that elevated corticosterone level during hypoxic exposure causes neurodegeneration and acts through its binding to GRs indicating that inhibition of GRs may provide therapeutic effect in ameliorating HH induced memory impairment.

Keywords: Corticosterone, memory impairment, hypobaric hypoxia, apoptosis, neurodegeneration

Volume 44

Society for Endocrinology BES 2016

Brighton, UK
07 Nov 2016 - 09 Nov 2016

Society for Endocrinology 

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