Chronic Stress Causes Sex-Specific and Structure-Specific Alterations in Mitochondrial Respiratory Chain Activity in Rat Brain.

Chronic restraint stress (CRS) induces a variety of changes in brain function, some of which are mediated by glucocorticoids. The response to stress occurs in a sex-specific way, and may include mitochondrial and synaptic alterations. The synapse is highly dependent on mitochondrial energy supply, and when mitochondria become dysfunctional, they orchestrate cell death. This study aimed to investigate the CRS effects on mitochondrial respiratory chain activity, as well as mitochondrial potential and mass in cell body and synapses using hippocampus, cortex and striatum of male and female rats. Rats were divided into non-stressed (control) and stressed group (CRS during 40 days). Results showed that CRS increased complex I-III activity in hippocampus. We also observed an interaction between CRS and sex in the striatal complex II activity, since CRS induced a reduction in complex II activity in males, while in females this activity was increased. Also an interaction was observed between stress and sex in cortical complex IV activity, since CRS induced increased activity in females, while it was reduced in males. Glucocorticoid receptor (GR) content in cortex and hippocampus was sexually dimorphic, with female rats presenting higher levels compared to males. No changes were observed in GR content, mitochondrial potential or mass of animals submitted to CRS. It was concluded that CRS induced changes in respiratory chain complex activities, and some of these changes are sex-dependent: these activities are increased in the striatal mitochondria by CRS protocol mainly in females, while in males it is decreased.

Mitochondrial and Oxidative Stress Aspects in Hippocampus of Rats Submitted to Dietary n-3 Polyunsaturated Fatty Acid Deficiency After Exposure to Early Stress.

Chronic dietary long-chain polyunsaturated fatty acids (PUFAs) deficiency may lead to changes in cortex and hippocampus neuronal membrane phospholipids, and may be linked to impaired central nervous system function. Particularly docosahexaenoic acid deficiency appears to be involved in neuropsychiatric disorders. On the other hand, adverse events early in life may also profoundly affect brain development, leading to long-lasting effects on neurophysiology, neurobiology and behavior. This research assessed if neonatal stress and a dietary n-3 PUFAs deficiency could interact to produce hippocampal alterations related to mitochondrial functions in adult rats. There were no effects of diet, neonatal intervention or interactions on superoxide dismutase or catalase enzymatic activities, mitochondrial membrane potential and respiratory chain complexes. Rats fed n-3 PUFAs deficient diet displayed higher levels of glutathione peroxidase and catalase activity, higher free radicals production and higher thiol content compared to rats fed n-3 PUFAs adequate diet. There were interactions among diets and neonatal stress, since glutathione peroxidase, free radicals production and thiol content were increased in groups that were subjected to neonatal interventions fed n-3 PUFAs deficient diet. Additionally, reduced mitochondrial potential was observed in handled animals. Total thiol revealed a neonatal stress effect, since animals subjected to neonatal interventions displayed lower thiol content. In conclusion, we observed that a chronic treatment with deficient n-3 PUFAs diet, from the puberty period on, increased free radicals production and imbalanced antioxidant enzymes activities, and these increases were higher in animals subjected to neonatal interventions.

Sex-dependent effect on mitochondrial and oxidative stress parameters in the hypothalamus induced by prepubertal stress and access to high fat diet.

OBJECTIVE: Some factors related to lifestyle, including stress and high-fat diet (HFD) consumption, are associated with higher prevalence of obesity. These factors can lead to an imbalance between ROS production and antioxidant defenses and to mitochondrial dysfunctions, which, in turn, could cause metabolic impairments, favoring the development of obesity. However, little is known about the interplay between these factors, particularly at early ages, and whether long-term sex-specific changes may occur. Here, we evaluated whether social isolation during the prepubertal period only, associated or not with chronic HFD, can exert long-term effects on oxidative status parameters and on mitochondrial function in the whole hypothalamus, in a sex-specific manner. METHODS: Wistar male and female rats were divided into two groups (receiving standard chow or standard chow + HFD), that were subdivided into exposed or not to social isolation during the prepubertal period. Oxidative status parameters, and mitochondrial function were evaluated in the hypothalamus in the adult age. RESULTS: Regarding antioxidant enzymes activities, HFD decreased GPx activity in the hypothalamus, while increasing SOD activity in females. Females also presented increased total thiols; however, non-protein thiols were lower. Main effects of stress and HFD were observed in TBARS levels in males, with both factors decreasing this parameter. Additionally, HFD increased complex IV activity, and decreased mitochondrial mass in females. Complex I-III activity was higher in males compared to females. CONCLUSION: Stress during the prepubertal period and chronic consumption of HFD had persistent sex-specific effects on oxidative status, as well as on its consequences for the cell and for mitochondrial function. HFD had more detrimental effects on females, inducing oxidative imbalance, which resulted in damage to the mitochondria. This HFD-induced imbalance may be related to the development of obesity.

Índice cintura-talla e índice de masa corporal como predictores de riesgo cardiometabólico en niños y adolescentes / Waist size index and body mass index as predictors of cardiometabolic risk in children and adolescents

Objetivo: comparar la utilidad del índice cintura-talla y el índice de masa corporal para detectar factores de riesgo cardiometabólicos en niños de 5-18 años, atendidos en la consulta externa del Hospital Infantil Regional Universitario Doctor Arturo Grullón en el período octubre-diciembre del año 2016. Método: se realizó un estudio observacional, comparativo, de corte transversal y fuente primaria, con una muestra de 118 pacientes. Se midieron las variables sociodemográficas (edad y sexo), antropométricas (peso, talla, IMC, ICT, PC, TA), y laboratorios (glicemia, ALT, colesterol, triglicéridos, HDL, LDL). Para el análisis cuantitativo se calculó el promedio y la desviación estándar, para el análisis cualitativo se utilizó la prueba estadística chi-cuadrado. Resultados: tanto el ICT como el IMC detectan de manera similar las alteraciones de la presión arterial sistólica (ICT=15.9 %, IMC=15 %), diastólica (ICT=20.4 %, IMC= 21.8 %), obesidad (ICT=69.5 %, IMC=73.7 %), HDL (ICT=6.8 %, IMC=5.6 %). En relación a la evaluación de la obesidad ambos índices arrojaron resultados afines, 69.5 % para ICT y 73.7 % el IMC. En la valoración de los niveles altos de ALT se obtuvieron resultados similares, presentando el ICT un 8.1 % y el IMC un 8.9 %. Conclusión: se demostró que tanto el ICT como el IMC son buenos predictores de factores de riesgos cardiometabólicos.

Objective: To compare the utility of the WSI and BMI in detecting cardiometabolic risks on children between 5-18 years, during external consult in Hospital Infantil Regional Universitario Dr. Arturo Grullón in the period of October-December 2016. Methods: A cross-sectional, primary source, observational design study was conducted with a sample of 118 patients. The variables measured for this study included sociodemographic (age and sex), anthropometric (weight, height, BMI, ICT, PC), and laboratories (glycemia, ALT, cholesterol, triglycerides, HDL, LDL). The quantitative analysis was carried out by calculating the average and the standard deviation. As for the qualitative analysis, the statistical test χ² was used. Results: Both the WSI and the BMI proved to be effective in detecting changes in Systolic (WSI = 15.9%, BMI = 18.4%) and Diastolic Blood Pressure (WSI = 20.4%, BMI = 18.6%), obesity (WSI = 69.5%, BMI = 73.7%), HDL (WSI = 29.3%, BMI = 29.9%). Regarding the detection of obesity, both rates showed similar results, 69.5% for ICT, and 73.7% for BMI. Comparable results were obtained in the assessment of high levels of ALT, with the ICT at 8.1% and the BMI at 8.9%. Conclusions: WSI and BMI are both useful to detect cardiometabolic risk factors.

Neonatal hypoxia-ischemia induces sex-related changes in rat brain mitochondria.

The effects of neonatal hypoxia-ischemia (HI) on energy metabolism in male and female rats were investigated, testing the hypothesis that HI-induced brain mitochondrial dysfunction could present in a dimorphic pattern. Impairment in electron transport chain complex activities at 2 and 18 h after HI was observed in cortex and hippocampus in rats of both sexes, with females presenting an overall activity higher than that of males. Females also showed loss of mitochondrial mass and membrane potential 18 h after HI, while males were only slightly affected. These findings suggest a dimorphism in mitochondrial dysfunction and provide information that may lead to new neuroprotection strategies.