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Enriched Environment Prevents Hypobaric Hypoxia Induced Neurodegeneration and is Independent of Antioxidant Signaling

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Abstract

Hypobaric hypoxia (HH) induced neurodegeneration has been attributed to several factors including increased oxidative stress, glutamate excitotoxicity, decreased growth factors, apoptosis, etc. Though enriched environment (EE) has been known to have beneficial effects in various neurological disorders, its effect on HH mediated neurodegeneration remains to be studied. Therefore, the present study was conducted to explore the effect of EE on HH induced neurodegeneration. Male Sprague–Dawley rats were placed in enriched and standard conditions during exposure to HH (7 days) equivalent to an altitude of 25,000 ft. The effect of EE on oxidative stress markers, apoptosis, and corticosterone level in hippocampus was investigated. EE during exposure to HH was found to decrease neurodegeneration as evident from decreased caspase 3 expression and LDH leakage. However, no significant changes were observed in ROS, MDA, and antioxidant status of hippocampus. HH elevates corticosterone level and affected the diurnal corticoid rhythm which may contribute to neurodegeneration, whereas EE ameliorate this effect. Because of the association of neurotrophins and stress and/or corticosterone the BDNF and NGF levels were also examined and it was found that HH decreases their level but concurrent exposure to EE maintains their level. Moreover, inhibition of Tyrosine kinase receptor (Trk) with K252a nullifies the protective effect of EE, whereas Trk activation with agonist, amitriptyline showed protective effect similar to EE. Taken together, we conclude that EE has a potential to ameliorate HH mediated neuronal degeneration which may act through antioxidant independent pathway by modulation of neurotrophins.

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Abbreviations

HA:

High altitude

HH:

Hypobaric hypoxia

HI:

Hypoxia-ischemia

EE:

Enriched Environment

BDNF:

Brain derived neurotrophic factor

NGF:

Nerve growth factor

ROS:

Reactive oxygen species

RNS:

Reactive nitrogen species

MDA:

Malondialdehyde

LDH:

Lactate dehydrogenase

GSH:

Glutathione

GSSG:

Glutathione disulfide

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GST:

Glutathione s-transferase

Trk:

Tyrosine kinase

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Acknowledgment

The study was fully supported by Defence Research and Development Organization (DRDO), Ministry of Defence India.

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Authors and Affiliations

  1. Department of Neurobiology, Defence Institute of Physiology and Allied Sciences (DIPAS), DRDO, Lucknow Road, Timarpur, Delhi, 110 054, India

    Vishal Jain, Iswar Baitharu, Dipti Prasad, Shashi Bala Singh & G. Ilavazhagan

  2. Department of Neurobiology, Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, India

    Kalpana Barhwal

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  1. Vishal Jain
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  2. Iswar Baitharu
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  3. Kalpana Barhwal
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  4. Dipti Prasad
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  6. G. Ilavazhagan
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Correspondence to G. Ilavazhagan.

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Jain, V., Baitharu, I., Barhwal, K. et al. Enriched Environment Prevents Hypobaric Hypoxia Induced Neurodegeneration and is Independent of Antioxidant Signaling. Cell Mol Neurobiol 32, 599–611 (2012). https://doi.org/10.1007/s10571-012-9807-5

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  • DOI: https://doi.org/10.1007/s10571-012-9807-5

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