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.
Chronobiology plays a crucial role in modulating many physiological systems in which there is nutritional synergism with meal timing. Given that intermitting fasting (IF) has grown as a flexible dietary method consisting of delayed or early eating windows, this scoping review addresses the effects of IF protocols on metabolism as they relate to clinical nutrition and the circadian system. While nocturnal habits are associated with circadian misalignments and impaired cardiometabolic profile – and nutritional physiology is better orchestrated during the day – most findings are based on animal experiments or human studies with observational designs or acute meal tests. Well-controlled randomized clinical trials employing IF protocols of delayed or early eating windows have sometimes demonstrated clinical benefits, such as improved glycemic and lipid profiles, as well as weight loss. However, IF does not appear to be more effective than traditional diets at the group level, and its effects largely depend on energy restriction. Thus, efforts must be made to identify patient biological rhythms, preferences, routines, and medical conditions before individual dietary prescription in clinical practice.
ABSTRACT. Schizophrenia and common mental disorders are noteworthy social and economic concern worldwide. Epidemiologic studies on the impact of specific mental disorders in emerging countries are scarce. Objectives: We aimed to characterize the demographic, social, and economic burden of schizophrenia and common mental disorders patients in the health system in Brazil. Methods: Data on these conditions in Brazil between 2008 and 2019 were collected through the website of the Departamento de Informática do Sistema Único de Saúde (Information Technology Department of the Unified Health System - DATASUS) maintained by the Brazilian Ministry of Health. Mean annual hospital admissions were 154,009.67, and cumulative incidence of 77.44 admissions per 100,000 inhabitants. Results: Average annual hospital expenses were US$ 67,216,056.04, with an average admission cost of US$ 432.58. The most affected age groups were older adults albeit younger individuals showed a trend towards increase of occurrences in recent years. There were a higher number of admissions in men compared to women. Conclusions: We consider the results obtained important to assist in evaluating and guiding public policies regarding the prevention and treatment in health systems.
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