Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.

Khushbu Jain,Ekta Kohli,Dipti Prasad,Shashi Bala Singh

doi:10.1155/2015/742059

Abstract

Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission) along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH). The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψ m, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission) and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

Highlights

Diminished ambient oxygen pressure at high altitude (HA) causes detrimental effects on central nervous system
In conclusion we have demonstrated the imbalance of mitochondrial fusion fission proteins in hippocampus leading to neurodegeneration
Fission predominates over fusion during oxygen deprivation and mitochondrial fragmentation occurs in hippocampal neurons

Summary

Introduction

Diminished ambient oxygen pressure at high altitude (HA) causes detrimental effects on central nervous system. Neurodegeneration is one of the major predicaments arising through hypobaric hypoxia (HH) [1] predominantly localized to hippocampus [2]. Oxygen and nitrogen free radical generation, energy dissipation, distorted neurotransmission (glutamate excitotoxicity), elevated corticosterone level, apoptosis, and alteration of genetic and proteomic functions are robust correlate of HH-associated neurodegeneration [3, 4]. Previous studies from our lab pointed out that intense HH exposure causes damage to neurons in rat brain hippocampus. Scientific literature has limited information on the effect of HH on essential organelles such as nucleus, mitochondria, and endoplasmic reticulum, in neurons. Mitochondria are vital organelle which plays an elementary role to provide ATP for regular brain functions [5, 6]

Methods

Results

Discussion

Conclusion