Mitochondrial function in rat cerebral cortex and hippocampus after short- and long-term hypobaric hypoxia

Czerniczyniec, Analía; Padula, Pablo La; Bustamante, Juanita; Karadayian, Analía G.; Lores‐Arnaiz, Silvia; Costa, Lidia E.

doi:10.1016/j.brainres.2014.12.018

Cited by 15 publications

(5 citation statements)

References 46 publications

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“…We found that mitochondria of the hippocampus, generally consumed oxygen and synthesized ATP at lower rates, when compared to mitochondria of the other two regions. These observations of low hippocampal oxygen consumption is in line with several other reports of isolated mitochondria (Burtscher et al, 2015;Cardoso et al, 2010;Czerniczyniec et al, 2015;Dagani et al, 1988;Sims, 1990;Varela et al, 2016) and brain homogenates (Sims, Finegan, & Blass, 1986;Sims & Pulsinelli, 1987). However, it was also observed that hippocampal mitochondria exhibited comparable ATP/O 2 ratios to the other regions, suggesting an overall general lower mitochondrial activity in this region (Dagani et al, 1988).…”

Section: Regional Differences In Mitochondrial Ocr and Atp Synthesisupporting

confidence: 91%

“…Compared to the literature, these values signify well-functioning mitochondria, validating the quality of our preparation (Burtscher, Zangrandi, Schwarzer, & Gnaiger, 2015;Cardoso, Santos, Seica, & Moreira, 2010;Czerniczyniec et al, 2015;Dagani et al, 1988;Lai et al, 1977;Sauerbeck et al, 2011;Sims, 1990;Varela, Schwartz, & Horvath, 2016). We observed that hippocampal mitochondria exhibited a larger proton leak, with both substrate conditions, resulting in reduced RCR values for this region.…”

Section: Mitochondrial Isolation and Functionsupporting

confidence: 84%

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Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non‐synaptic mouse brain mitochondria

Andersen

Jakobsen

Waagepetersen

2019

J of Neuroscience Research

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Brain mitochondrial dysfunction has been implicated in several neurodegenerative diseases. The distribution and efficiency of mitochondria display large heterogeneity throughout the regions of the brain. This may imply that the selective regional susceptibility of neurodegenerative diseases could be mediated through inherent differences in regional mitochondrial function. To investigate regional cerebral mitochondrial energetics, the rates of oxygen consumption and adenosine‐5′‐triphosphate (ATP) synthesis were assessed in isolated non‐synaptic mitochondria of the cerebral cortex, hippocampus, and striatum of the male mouse brain. Oxygen consumption rates were assessed using a Seahorse XFe96 analyzer and ATP synthesis rates were determined by an online luciferin‐luciferase coupled luminescence assay. Complex I‐ and complex II‐driven respiration and ATP synthesis, were investigated by applying pyruvate in combination with malate, or succinate, as respiratory substrates, respectively. Hippocampal mitochondria exhibited the lowest basal and adenosine‐5′‐diphosphate (ADP)‐stimulated rate of oxygen consumption when provided pyruvate and malate. However, hippocampal mitochondria also exhibited an increased proton leak and an elevated relative rate of oxygen consumption in response to the uncoupler carbonyl cyanide 4‐(trifluoromethoxy)phenylhydrazone (FCCP), showing a large capacity for uncoupled respiration in the presence of pyruvate. When the complex II‐linked substrate succinate was provided, striatal mitochondria exhibited the highest respiration and ATP synthesis rate, whereas hippocampal mitochondria had the lowest. However, the mitochondrial efficiency, determined as ATP produced/O2 consumed, was similar between the three regions. This study reveals inherent differences in regional mitochondrial energetics and may serve as a tool for further investigations of regional mitochondrial function in relation to neurodegenerative diseases.

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Section: Regional Differences In Mitochondrial Ocr and Atp Synthesisupporting

confidence: 91%

Section: Mitochondrial Isolation and Functionsupporting

confidence: 84%

Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non‐synaptic mouse brain mitochondria

Andersen

Jakobsen

Waagepetersen

2019

J of Neuroscience Research

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“…It has been widely reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and respiratory diseases, as well as central nervous system diseases [2,3]. However, despite these potential beneficial effects of the hypoxic condition, no studies to date have investigated the effects of hypoxia on osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis

Wang

Sun

et al. 2016

Med Sci Monit

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BackgroundAlthough it has been reported that hypoxic exposure can attenuate hypertension, heart disease, diabetes, and some other diseases, effects of hypoxia on osteoporosis are still unknown.Material/MethodsThe current study investigated whether short-term hypoxic exposure (in comparison with normoxic conditions) affects bone metabolism in normal or ovariectomized (OVX) adult female rats in an vivo study. Micro-computed tomography bone volume/structural analyses, histological examination, and serum bone turnover biochemical assays were used. In addition, the expressions of some associated major regulatory molecules were measured in osteoblastic cultures.ResultsWhile the 14-day hypoxic exposure did not change the bone-remodeling process in normal adult female rats, it decreased bone volume, osteoclast density, and serum bone formation marker (alkaline phosphatase) level, but increased osteoclast density and serum bone resorption marker (C-telopeptide of collagen) level in OVX rats. The bone marrow adipocyte number and serum fatty acid binding protein-4 level were increased in OVX-hypoxic rats compared with OVX-normoxic rats. Consistently, in human MG-63 osteoblastic cultures, the hypoxic condition suppressed protein expression of osteogenic transcriptional factors Runx2 and osterix, elevated protein expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand, but reduced that of osteoclastogenic inhibitor osteoprotegerin.ConclusionsOur results suggest that, although no change occurred in the bone-remodeling process in normal adult female rats after hypoxic exposure, under the estrogen-deficient osteoporotic condition, the hypoxic condition can alter the bone microenvironment so that it may further impair osteoblastic differentiation and enhance osteoclastic formation, and thus reduce bone formation, enhance bone resorption, and accelerate bone loss.

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“…The expression of nNOS and HO-1 mRNA was also enhanced in male CHH-exposed rats, indicating that oxidative stress and immune system disorder were occurring in the CNS (central nervous system) of CHH-exposed rats. HO-1 is particularly sensitive to the induction of cytokines, oxidants, and other stressors ( Schipper et al, 2009 ) and nNOS can induce an increase in nitric oxide production in the CNS ( Czerniczyniec et al, 2015 ). Besides, the expression of nNOS is directly related to glutamate.…”

Section: Discussionmentioning

confidence: 99%

The role of sex and ovarian hormones in hippocampal damage and cognitive deficits induced by chronic exposure to hypobaric hypoxia

Zhu

Zhang²,

He³

et al. 2022

Front. Neurosci.

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PurposeThis study aims to investigate the role of sex and ovarian hormones in hippocampal damage and cognitive deficits and behavioral dysfunction in rats induced by chronic exposure to hypobaric hypoxia.MethodsSix-week-old male and female SD rats were housed for 3 months either in a real altitude (4,250 m) environment as the model of chronic hypobaric-hypoxia (CHH) or in a plain as controls. The animal behavioral and hippocampal neurons at subcellular, molecular, and ultrastructural levels were characterized after CHH exposure.ResultsAfter 3 months of CHH exposure, (1) male CHH rats’ serum testosterone level was lower than male controls’ whereas female CHH rats’ serum estradiol level was higher than female controls’; (2) Morris water maze test finds that male rats showed more learning and spatial memory deficits than female rats; (3) male rats showed more severe hippocampal damage, hippocampal inflammation, oxidative stress and decreased hippocampal integrity (neurogenesis and dendritic spine density) than female rats; (4) Western blot analysis shows that, compared with the male control group, in male CHH group’s hippocampus, expression of nNOS, HO-1, and Bax protein increased whereas that of Bcl-2 protein decreased; (5) Expression of PON2 protein in male rats (CHH and controls) was lower than female rats (CHH and controls). In addition, CHH exposure decreased the expression of PON2 protein in both male and female rats; (6) qPCR analysis reveals that CHH exposure reduced the gene expression of N-methyl-D-aspartate receptor NR2A and NR2B subunits in male rats’ hippocampus. In addition, compared with the sham CHH group, the expression level of PON2 protein decreased in the OVX-CHH group’s hippocampus whereas oxidative stress, neuroinflammation, and degeneration of hippocampal neurons increased in the OVX-CHH group’s hippocampus.ConclusionAfter CHH exposure, male rats were significantly more likely than female rats to develop hippocampal damage, hippocampal neuroinflammation, and cognitive decline and deficits, suggesting that sex and ovarian hormones were significantly involved in regulating the rats’ susceptibility to CHH exposure-induced hippocampal damage.

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Mitochondrial function in rat cerebral cortex and hippocampus after short- and long-term hypobaric hypoxia

Cited by 15 publications

References 46 publications

Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non‐synaptic mouse brain mitochondria

Distinct differences in rates of oxygen consumption and ATP synthesis of regionally isolated non‐synaptic mouse brain mitochondria

Short-Term Hypoxia Accelerates Bone Loss in Ovariectomized Rats by Suppressing Osteoblastogenesis but Enhancing Osteoclastogenesis

The role of sex and ovarian hormones in hippocampal damage and cognitive deficits induced by chronic exposure to hypobaric hypoxia

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