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Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.

Jain K, Prasad D, Singh SB, Kohli E - Neurol Res Int (2015)

Bottom Line: The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days.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.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Lab, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Ministry of Defence, Government of India, Lucknow Road, Timarpur, Delhi 110054, India.

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.

No MeSH data available.


Related in: MedlinePlus

(a) Representative electron micrograph of hippocampal CA1 region shows temporal alteration in mitochondrial morphology and graphical representation showed changes in (b) mitochondrial length and (c) number. ∗ denotes p < 0.05 compared to Cntrl. Data are expressed as mean ± SD; n = 3. Bar depicted in the figures is equivalent to 50 nm, 1 μm, and 100 nm in length.
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fig3: (a) Representative electron micrograph of hippocampal CA1 region shows temporal alteration in mitochondrial morphology and graphical representation showed changes in (b) mitochondrial length and (c) number. ∗ denotes p < 0.05 compared to Cntrl. Data are expressed as mean ± SD; n = 3. Bar depicted in the figures is equivalent to 50 nm, 1 μm, and 100 nm in length.

Mentions: TEM imaging revealed the change in mitochondrial morphology after HH exposure with all time points. Short, round mitochondria with distorted cristae were observed in HH exposed neurons with significant change at 7 dHH exposure. Moderate changes in mitochondrial structure were also observed in 21 dHH and 28 dHH rat brain mitochondria. Quantitative analysis reveals that mitochondria found in Cntrl rat's hippocampus are 1-2 μm in length as compared to 7 dHH and 14 dHH exposed rats, where ≤0.5–1 μm mitochondria are present (Figure 3). CA3 region also showed same type of mitochondrial morphology with HH exposure compared to Cntrl (data not shown).


Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.

Jain K, Prasad D, Singh SB, Kohli E - Neurol Res Int (2015)

(a) Representative electron micrograph of hippocampal CA1 region shows temporal alteration in mitochondrial morphology and graphical representation showed changes in (b) mitochondrial length and (c) number. ∗ denotes p < 0.05 compared to Cntrl. Data are expressed as mean ± SD; n = 3. Bar depicted in the figures is equivalent to 50 nm, 1 μm, and 100 nm in length.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4509498&req=5

fig3: (a) Representative electron micrograph of hippocampal CA1 region shows temporal alteration in mitochondrial morphology and graphical representation showed changes in (b) mitochondrial length and (c) number. ∗ denotes p < 0.05 compared to Cntrl. Data are expressed as mean ± SD; n = 3. Bar depicted in the figures is equivalent to 50 nm, 1 μm, and 100 nm in length.
Mentions: TEM imaging revealed the change in mitochondrial morphology after HH exposure with all time points. Short, round mitochondria with distorted cristae were observed in HH exposed neurons with significant change at 7 dHH exposure. Moderate changes in mitochondrial structure were also observed in 21 dHH and 28 dHH rat brain mitochondria. Quantitative analysis reveals that mitochondria found in Cntrl rat's hippocampus are 1-2 μm in length as compared to 7 dHH and 14 dHH exposed rats, where ≤0.5–1 μm mitochondria are present (Figure 3). CA3 region also showed same type of mitochondrial morphology with HH exposure compared to Cntrl (data not shown).

Bottom Line: The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days.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.

View Article: PubMed Central - PubMed

Affiliation: Neurobiology Lab, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Ministry of Defence, Government of India, Lucknow Road, Timarpur, Delhi 110054, India.

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.

No MeSH data available.


Related in: MedlinePlus