Traumatic brain injury (TBI) increases Ca 2+ influx into neurons and desynchronizes mitochondrial function leading to energy depletion and apoptosis. This process may be influenced by brain testosterone (TS) levels, which are known to decrease after TBI. We hypothesized that a TS-based therapy could preserve mitochondrial neuroenergetics after TBI, thereby reducing neurodegeneration. C57BL/6J mice were submitted to sham treatment or severe parasagittal controlled cortical impact (CCI) and were subcutaneously injected with either vehicle (VEH-SHAM and VEH-CCI) or testosterone cypionate (15 mg/kg, TS-CCI) for 10 days. Cortical tissue homogenates ipsilateral to injury were used for neurochemical analysis. The VEH-CCI group displayed an increased Ca 2+-induced mitochondrial swelling after the addition of metabolic substrates (pyruvate, malate, glutamate, succinate, and adenosine diphosphate [PMGSA]). The addition of Na + stimulated mitochondrial Ca 2+ extrusion through Na + /Ca 2+ /Li + exchanger (NCLX) in VEH-SHAM and TS-CCI, but not in the VEH-CCI group. Reduction in Ca 2+ efflux post-injury was associated with impaired mitochondrial membrane potential formation/dissipation, and decreased mitochondrial adenosine triphosphate (ATP)-synthase coupling efficiency. Corroborating evidence of mitochondrial uncoupling was observed with an increase in H 2 O 2 production post-injury, but not in superoxide dismutase (SOD2) protein levels. TS administration significantly reduced these neuroenergetic alterations. At molecular level, TS prevented the increase in pTau Ser396 and alpha-Spectrin fragmentation by the Ca 2+ dependent calpain-2 activation, and decreased both caspase-3 activation and Bax/BCL-2 ratio, which suggests a downregulation of mitochondrial apoptotic signals. Search Tool for the Retrieval of Interacting Genes/Proteins database provided two distinct gene/protein clusters, ''upregulated and downregulated,'' interconnected through SOD2. Therefore, TS administration after a severe CCI improves the mitochondrial Ca 2+ extrusion through NCLX exchanger and ATP synthesis efficiency, ultimately downregulating the overexpression of molecular drivers of neurodegeneration.
Comparison between resting metabolic rate and indirect calorimetry in postmenopausal women
Comparação de equações preditivas de taxa metabólica de repouso com calorimetria indireta em mulheres pós-menopáusicasÁlvaro REISCHAK-OLIVEIRA 2
Revista de NutriçãoRev. Nutri., Campinas, 30 (5):583-591, set./out., 2017 https://doi.org/10.1590/1678-98652017000500004 582 RB CARTERI et al.
ConclusionThis study suggests that differences in body composition in postmenopausal women influence the accuracy of predictive equations, demonstrating the need for more accurate estimation methods for resting metabolic rate in postmenopausal women with different body compositions.Keywords: Basal metabolism. Calorimetry indirect. Menopause.
R E S U M O
ObjetivoComparar os valores de taxa metabólica de repouso determinados por calorimetria indireta com os valores obtidos utilizando diferentes equações preditivas em mulheres pós-menopausicas eutróficas e com sobrepeso.
MétodosVinte e quatro mulheres com pelo menos dois anos de menopausa foram submetidas à avaliações antropométricas e à calorimetria indireta após 12 horas de jejum para determinar, matematicamente e experimentalmente, a taxa metabólica de repouso.
ResultadosOs valores para calorimetria indireta não diferiram entre os grupos e a taxa metabólica de repouso predita por equações foi diferente para todas as equações usadas. Para o grupo de eutróficas, as equações que não foram estatisticamente diferentes da calorimetria indireta foram Food and Agricultural Organization, Fredix, Lazzer e Schofield. No entanto, apenas as equações Berstein e Owen foram significativamente diferentes comparadas com calorimetria indireta para o grupo sobrepeso.
ConclusãoO presente estudo sugere que diferenças na composição corporal em mulheres na pós-menopausa modificam a precisão de equações que predizem a taxa metabólica de repouso, demonstrando a necessidade de aprimorar métodos de estimação de taxa metabólica de repouso em mulheres pós-menopáusicas com diferentes composições corporais.
Palavras-chave: Metabolismo basal. Calorimetria indireta. Menopausa. RESTING METABOLIC RATE IN POSTMENOPAUSE 583
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