Rat Brain Mitochondrial Function Research Articles

Effects Of PHB1 Changes In Different Exercise Models On Brain Mitochondrial Function And Energy Metabolism In Rats

PURPOSE: ATP synthesis plays the most important role. ATP synthesis is closely related to the structural and functional integrity of mitochondria. To investigate the effects of PHB1 expression changes on brain mitochondrial function in rats of different exercise modes. METHODS: 160 healthy male SD rats were randomly divided into four groups: normal control(NC),moderate intensity exercise(MIE),excessive fatigue exercise(EFE), and acute exhaustive exercise(AEE) groups.NC and AEE:routinely raised.MIE: 10 minutes per day at 10 m/min for the first week and increased for 10 minutes every day until the end of the second week.From the third week, rats run at 15 m/min for 60 min every day until the end of the 8th week. Slope:10%. EFE: From the first week of training, the speed of the running platform is 15 m/min, increased by 5 m/min per week to 30 m/min.Training time is 30 minutes and increased by 20 minutes per week until 110 minutes. Slope: increase by 5% per week until 15%. The EFE and AEE groups were trained for 6 days per week for 8 weeks. AEE:The rats were subjected to acute exhaustive exercise after 8 weeks. They were killed after 48 h of the last experiment. Mitochondrial respiratory control rate (RCR), ATP content, ROS level, complex V activity and PHB1 expression were measured. RESULTS: Compared with NC, in MIE group , RCR (+87%,P < 0.001), ATP content (+56%,P < 0.05), complex V activity (+81%,P < 0.05), PHB1 expression (+42%,P < 0.01) were increased, and ROS level (-67%,P < 0.001)was reduced; In EFE group , RCR (-43%,P < 0.01), ATP content (+53%,P < 0.05), complex V activity (+89%, P < 0.001), PHB1 expression (+28%,P < 0.01) and ROS level (+62%, P < 0.001) were increased; In AEE group ,the RCR (-78%, P < 0.05), ATP content (-75%,P < 0.05), complex V activity (-83%,P < 0.001), PHB1 expression (-35%,P < 0.01)decreased, and ROS (+96%,P < 0.05)level increased. Correlation analysis showed that PHB1 expression was positively correlated with ATP content in three groups. CONCLUSIONS: Changes in PHB1 expression brain tissue were consistent with changes in mitochondrial function under different motion modes.It is suggested that there may be interaction between PHB1 and ATP synthase. PHB1 participates in the stabilization of brain mitochondrial structure, changes mitochondrial function and affects the body's ability to exercise.

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function.

Age and Sex-Related Changes in Rat Brain Mitochondrial Function

Aging is responsible for the decline in the function of mitochondria and their increase in size and number - adaptive mechanism to restore mitochondrial function. Estrogens increase mitochondrial function, especially in female rats. The aim of this study was to determine the age-related changes in rat brain mitochondrial function focusing on sex differences. Cellular and mitochondrial protein and DNA content, mitochondrial oxidative and phosphorylative function in male and female rat brain from four different age groups (6, 12, 18 and 24 months old) were analyzed. Mitochondria protein/DNA content decreased with aging shifting toward lesser mitochondrial functional capacity and the mitochondria number increased. A sex dimorphism was determined, with female rat brain showing mitochondria with greater functional capacity than males. These sex differences gradually increased during aging.

Low-molecular-mass peptides from the venom of the Amazonian viper Bothrops atrox protect against brain mitochondrial swelling in rat: Potential for neuroprotection

The neurodegenerative diseases are important causes of morbidity and mortality in Western countries. Common mechanisms of toxicity involving mitochondrial damage have been suggested; however, a definitive treatment has not yet been found. Therefore, there has been great interest in the development of mitochondria-targeted protective compounds for the treatment of neuropathies. Animal toxins represent a promising source of new molecules with neuroprotective activity and potential to originate new drugs. We present here the effects of a low-molecular-mass peptides fraction (Ba-V) from Bothrops atrox snake venom, on rat brain mitochondrial function. Ba-V did not induce the mitochondrial swelling and moreover, was as effective as cyclosporin A (CsA) to inhibit the calcium/phosphate-induced swelling, which indicates its potential to prevent the mitochondrial permeability transition (MPT). The membrane electrochemical potential, the oxygen consumption during states-3 and -4 respirations as well as the respiratory control ratio (RCR) were not affected by Ba-V. Additionally, Ba-V did not induce reactive oxygen species (ROS) generation. Interestingly, Ba-V did not protect against the generation of ROS induced by t-BOH, which suggests a protection mechanism other than ROS scavenging. Given the important role of the mitochondrial damage and, more specifically, of MPT, in the development of neuropathies, Ba-V might be useful in the future strategies for the treatment of these diseases.

Sex-dependent differences in aged rat brain mitochondrial function and oxidative stress

Females show lower incidences of several neurodegenerative diseases related to oxidative stress and mitochondrial dysfunction than males. In addition, female rats show more differentiated mitochondria than males in several tissues. The aim of this work was to investigate the existence of sex-dependent differences in brain mitochondrial bioenergetics and oxidative balance in aged rats. Results showed that aged female rat brain had a lower mitochondria content than aged male brain but with a greater differentiation degree given the higher mitochondrial protein content and mitochondrial complex activities in females. Female rat brain also showed a better oxidative balance than that of males, reflected by the fact that higher mitochondrial respiratory chain function is accompanied by a similar ROS production and greater antioxidant enzyme activities, which could be responsible for the lesser oxidative damage observed in proteins and lipids in this sex. Interestingly, levels of UCP4 and UCP5—proteins related to a decrease in ROS production—were also higher in females. In conclusion, aged female rat brain had more differentiated mitochondria than male brain and showed a better control of oxidative stress balance, which could be due, in part, to the neuroprotective effect of UCPs.

Dactylorhin B reduces toxic effects of β-amyloid fragment (25–35) on neuron cells and isolated rat brain mitochondria

beta-amyloid is strongly implicated in Alzheimer's pathology, and mitochondria play an important role in neurodegenerative disorders. Dactylorhin B [short for bis(4-beta-D-glucopyranosyloxybenzyl)-2-beta-D-glucopyranosyl-2-isobutyltartrate (DHB)] is an active compound isolated from Coeloglossum viride. (L.) Hartm. var. bracteatum (Willd.) and may have neuroprotective effects. In the present study, we investigated the damage of rat brain mitochondrial function induced by beta-amyloid and the protective effect of DHB. Isolated rat brain mitochondria were incubated with amyloid-beta peptide (Abeta)(25-35) alone or together with DHB. reactive oxygen species production, pyruvate dehydrogenase complex activity, alpha-ketoglutarate dehydrogenase complex activity, cytochrome c oxidase activity, mitochondrial swelling, mitochondrial membrane potential and the release of cytochrome c from mitochondria were measured. Data showed that Abeta(25-35) directly disrupted mitochondrial function, inhibited the key enzymes and contributed to apoptosis and the deficiency of energy metabolism. Co-incubation of DHB attenuated Abeta(25-35)-induced pathological changes. The significance of DHB in the management of mitochondria-related disorders is discussed.

In vitro and in vivo effects of methyl isocyanate on rat brain mitochondrial respiration.

The present study deals with the in vitro and in vivo effects of methyl isocyanate (MIC) on rat brain mitochondrial function. Addition of MIC to tightly coupled brain mitochondria in vitro resulted in a mild stimulation of state 4 respiration, abolition of respiratory control, decrease in ADP/O ratio, and inhibition of state 3 oxidation. The oxidation of NAD(+)-linked substrates (glutamate + malate) was more sensitive (fourfold) to the inhibitory action of MIC than succinate while cytochrome oxidase was unaffected. Administration of MIC subcutaneously at a lethal dose affected respiration only with glutamate+malate as the substrate (site I) and caused a 20% decrease in state 3 oxidation leading to a significant decrease in respiratory control index while state 4 respiration and ADP/O ratio remained unaffected. As both the malondialdehyde and iron contents of brain mitochondria were not altered, it may be inferred that the observed in vivo inhibition of state 3 oxidation is induced by MIC through systemic stagnant hypoxia leading to ischemia of brain, which further contributes to the cerebral hypoxia.

Biochemistry and physiology of brain ammonia.

Biochemistry and physiology of brain ammonia.