Age‐related changes in regional brain mitochondria from Fischer 344 rats

LaFrance, R.; Brustovetsky, Nickolay; Sherburne, C.; DeLong, David J.; Dubinsky, Janet M.

doi:10.1111/j.1474-9726.2005.00156.x

Cited by 47 publications

(28 citation statements)

References 45 publications

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“…Recently, we showed that naïve F344 rats display no age-related deficits in mitochondrial respiration (Gilmer et al, 2010), therefore deficits may not be apparent until the mitochondria are challenged. Other data support these findings in F344 rats, including those that show that mitochondrial membrane potential and susceptibility to permeability transition was stable out to 24 months (LaFrance et al, 2005).…”

Section: Discussionmentioning

confidence: 58%

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Gilmer

Ansari

Roberts

et al. 2010

Journal of Neurotrauma

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Mitochondrial dysfunction is known to occur following traumatic brain injury (TBI) and has been well characterized. This study assessed possible age-related changes in the cortical mitochondrial bioenergetics following TBI. Three hours following a moderate TBI, tissue from the ipsilateral hemisphere (site of impact and penumbra) and the corresponding contralateral region were harvested from young (3-to 5-month-old) and aged (22-to 24-month-old) Fischer 344 rats. Synaptic and extrasynaptic mitochondria were isolated using a Ficoll gradient, and several bioenergetic parameters were examined using a Clark-type electrode. Injury-related respiration deficits were observed in both young and aged rats. Synaptic mitochondria showed an age-related decline in the rate of ATP production, and a decline in respiratory control ratios (RCR), which were not apparent in the extrasynaptic fraction. Following respiration analysis, mitochondrial samples were probed for oxidative damage (3-nitrotyrosine [3-NT], 4-hydroxynonenal [4-HNE], and protein carbonyls [PC]). All markers of oxidative damage were elevated with injury and age in the synaptic fraction, but only with injury in the extrasynaptic fraction. Synaptic mitochondria displayed the highest levels of oxidative damage and may contribute to the synaptic bioenergetic deficits seen following injury. Data indicate that cortical synaptic mitochondria appear to have an increased susceptibility to perturbation with age, suggesting that the increased mitochondrial dysfunction observed following injury may impede recovery in aged animals.

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Section: Discussionmentioning

confidence: 58%

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Gilmer

Ansari

Roberts

et al. 2010

Journal of Neurotrauma

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“…The drop mΔΨ in brain mitochondria of WKY and SHR rats due to the addition of Ca 2+ excess (160, 480, and 640 nmol Ca 2+ ) was restored by the addition of Ca 2+ chelating agents, this suggest that Ca 2+ excess did not cause mitochondrial damage, which would be attributed to the relative resistance of brain mitochondria to Ca 2+ overload. Accordingly, other studies found that depending on the brain region, mitochondria are differentially sensitive to Ca 2+ overload (LaFrance et al, 2005;Brown et al, 2006), without undergoing mitochondrial permeability transition (Berman et al, 2000).…”

Section: Discussionmentioning

confidence: 94%

Changes in mitochondrial functionality and calcium uptake in hypertensive rats as a function of age

et al. 2008

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We studied whether mitochondrial functions and Ca 2+ metabolism were altered in Wistar Kyoto normotensive (WKY) and spontaneous hypertensive rats (SHR). Ca 2+ uptake was decreased in SHR compared to WKY rats. Accumulation of Ca 2+ was more efficient in WKY than in SHR rats. mΔΨ was lower in SHR compared to WKY rats. Basal complex IV activity was higher in SHR than WKY rats, whereas basal L-citrulline production, an indicator of nitric oxide synthesis, was decreased in SHR and dependent on Ca 2+ concentration (p < 0.05). Impact of Ca 2+ was counteracted by EGTA. These data show an age-dependent decreased mitochondrial functions in brain mitochondria during hypertension.

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“…Liver mitochondria from old rats showed decreased membrane potential, an impairment that was improved by treatment with an antioxidant extract (139). Cortical and striatal mitochondria of aged rats showed lower membrane potentials with increased susceptibility to the permeability transition at advanced ages (88). Mitochondria isolated from thoraces of Drosophila melanogaster, mainly flight muscle mitochondria, showed a significant decrease in state 3 respiration, respiratory control ratios, and uncoupled respiration rates, as a function of age, using either NAD-or FAD-linked substrates, but there were no differences in state 4 respiration rates, which does not indicate increased H ϩ permeability in aging (51).…”

Section: Increased H ϩ Permeability Of the Inner Membranementioning

confidence: 99%

The mitochondrial energy transduction system and the aging process

Navarro¹,

Boveris²

2007

American Journal of Physiology-Cell Physiology

588

401

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Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292: C670 -C686, 2007; doi:10.1152/ajpcell.00213.2006.-Aged mammalian tissues show a decreased capacity to produce ATP by oxidative phosphorylation due to dysfunctional mitochondria. The mitochondrial content of rat brain and liver is not reduced in aging and the impairment of mitochondrial function is due to decreased rates of electron transfer by the selectively diminished activities of complexes I and IV. Inner membrane H ϩ impermeability and F1-ATP synthase activity are only slightly affected by aging. Dysfunctional mitochondria in aged rodents are characterized, besides decreased electron transfer and O 2 uptake, by an increased content of oxidation products of phospholipids, proteins and DNA, a decreased membrane potential, and increased size and fragility. Free radicalmediated oxidations are determining factors of mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and lifespan. Inner membrane enzyme activities, such as those of complexes I and IV and mitochondrial nitric oxide synthase, decrease upon aging and afford aging markers. The activities of these three enzymes in mice brain are linearly correlated with neurological performance, as determined by the tightrope and the T-maze tests. The same enzymatic activities correlated positively with mice survival and negatively with the mitochondrial content of lipid and protein oxidation products. Conditions that increase survival, as vitamin E dietary supplementation, caloric restriction, high spontaneous neurological activity, and moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain and liver. The pleiotropic signaling of mitochondrial H 2O2 and nitric oxide diffusion to the cytosol seems modified in aged animals and to contribute to the decreased mitochondrial biogenesis in old animals. oxidative damage; survival; complexes I and IV; nitric oxide synthase EARLY OBSERVATIONS by Leloir and Muñoz (92) indicated that fatty acid oxidation depends on a labile particulate material of liver homogenates. Later, Kennedy and Lehninger (82) reported that the oxidation of fatty acids and of citric acid cycle intermediates was carried out by osmotically active structures with coupled ADP phosphorylation to ATP. Simultaneously, Sjostrand (146) and Palade (126) recognized by electron microscopy the characteristic double membrane of mitochondria. The concept of oxidative phosphorylation as the mitochondrial function evolved from the confluence of structural and biochemical knowledge and by 1952, mitochondria were described by Lehninger (91) as intracellular "power plants".

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Age‐related changes in regional brain mitochondria from Fischer 344 rats

Cited by 47 publications

References 45 publications

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Age-Related Mitochondrial Changes after Traumatic Brain Injury

Changes in mitochondrial functionality and calcium uptake in hypertensive rats as a function of age

The mitochondrial energy transduction system and the aging process

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