Disfunción mitocondrial como mediador de muerte celular inducida por ketamina en células neuronales: efecto sobre el metabolismo del calcio mitocondrial
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ItemBrain cortex mitochondrial bioenergetics in synaptosomes and non-synaptic mitochondria during aging(Neurochemical research, 2016-1-28)Alterations in mitochondrial bioenergetics have been associated with brain aging. In order to evaluate the susceptibility of brain cortex synaptosomes and non-synaptic mitochondria to aging-dependent dysfunction, male Swiss mice of 3 or 17 months old were used. Mitochondrial function was evaluated by oxygen consumption, mitochondrial membrane potential and respiratory complexes activity, together with UCP-2 protein expression. Basal respiration and respiration driving proton leak were decresed by 26 and 33% in sunaptosomes from 17-months old mice, but spare respiratory rate was decreased by 45% in brain cortex non-synaptic mitochondria from 17-month-old mice, as compared with young animales, but respiratory control was not affected. Synaptosomal mitochondria would be susceptible to undergo calcium-induced depolarization in 17 months-old mice, while non synaptic mitochondrian would not be affectred by calcium overload. UCP2 was significantly up-regulated in both synaptosomal and submitochondrial membranes from 17-months old mice, compared to young animals. UCP-2 upregulation seems to be a possible mechanism by which mitochondria would be resistant to suffer oxidative damage during aging.
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ItemKetamine effect on intracellular and mitochondrial calcium mobilization(Biocell, 2016)The suppressive effects of ketamine on intracellular calcium has been reported in a variety of cells although the mechanisms involved are not well understood. The aim of this work was to evaluate the ketamine effect on the mitochondrial Ca2+ accumulation and the cellular Ca2+ mobilization using FLUO4-AM and flow cytometry. The results showed that mitochondria from ketamine injected animals presented a lower ability to retain calcium at concentrations higher than 20 µM, as compared with controls (saline injected animals). In addition, ketamine showed a significant decreased KCl-induced intracellular calcium concentration. KCl increased calcium influx through cellular depolarization. According to the data presented herein, ketamine presents a clear inhibitory effect on cytosolic Ca2+ transport mechanisms, independently from their action on the calcium channel associated NMDA receptor.
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ItemAlcohol hangover: impairments in behavior and bioenergetics in central nervous system(Biocell, 2016-4-16)Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when EtOH is absent in plasma. Results from our laboratory have shown behavioral impairments and mitochondrial dysfunction in an experimental model of AH in mice. Our model consisted in a single i.p. injection of EtOH (3.8 g/kg BW) or saline solution in male and female mice, sacrificing the animals 6 hours after injection. Motor and affective behavior together with mitochondrial function and free radical production were evaluated in brain cortex and cerebellum during AH. Results showed that hangover animals exhibited a significant reduction in neuromuscular coordination, motor strength and locomotion together with a loss of gait stability and walking deficiencies. Moreover, an increment in anxiety-like behavior together with fear-related phenotype and depression signs were observed. In relation to bioenergetics metabolism, AH induced a reduction in oxygen uptake, inhibition of respiratory complexes, changes in mitochondrial membrane permeability, decrease in transmembrane potential, increase in O2•- and H2O2 production and impairment in nitric oxide metabolism. All together our data suggest that the physiopathological state of AH involves behavioral impairments and mitochondrial dysfunction in mouse brain cortex and cerebellum showing the long lasting effects of acute EtOH exposure in CNS.