Acute exercise increases BDNF serum levels in patients with Parkinson's disease regardless of depression or fatigue.

Studies have consistently reported a decreased level of brain-derived neurotrophic factor (BDNF) in individuals with Parkinson's disease (PD). The benefits of exercise on BDNF levels are well-documented in humans, however, the effects of acute exercise are inconclusive in neurological disorders. In addition, there are no studies investigating a precursor molecule - proBDNF - and its comparison to patients with vs. without depression or fatigue. Thirty patients with PD were instructed to walk on a treadmill at light to moderate intensity for 30 min. Generalized Estimating Equation (GEE) showed a significant effect of time (pre- vs. post-exercise) when compared individuals with vs. without depression [Wald Chi Square (4.392), p = 0.036)] and with vs. without fatigue [Wald Chi Square (7.123), p = 0.008)] for mature BDNF (mBDNF) level. There was no effect of group, time, and group x time interaction for proBDNF level when compared individuals with vs. without depression or fatigue. The present study showed that a single bout of light to moderate-intensity exercise increases mBDNF serum levels in patients with PD regardless of depression and fatigue. Our finding is important because it is necessary investigate methods to enhance the gains made by rehabilitation, especially when considering a short period of rehabilitation in different health services. The increase in mBDNF level can lead to an enhancement of neuroplasticity and facilitate the improvement of motor performance. No effect on proBDNF level could be explained, as this precursor molecule is cleaved by intracellular or extracellular enzymes.

Functional mobility in Parkinson's disease: associations with motor and non-motor symptoms / Mobilidade funcional em indivíduos com doença de Parkinson: associações com alterações motoras e não motoras

Functional mobility (FM) is the ability of people to move in different environments, including at home, at work, and in the community, in order to perform functional activities or tasks, independently and safely. Objective: The aim of the present study was to investigate which motor and/or non-motor symptoms (severity of the motor symptoms, depressive symptoms, and fatigue) have the greatest impact on FM assessed by Modified Parkinson Activity Scale (mPAS) in individuals with Parkinson's disease (PD). Method: The outcome of interest was FM assessed by mPAS, which includes 14 activities covering three domains (chair transfers, gait akinesia, and bed mobility). Unified Parkinson's Disease Rating Scale (UPDRS) Part III, Beck Depression Inventory (BDI), and Parkinson's Disease Fatigue Scale-16 (PFS-16) were used. Results: Forty-four individuals (age: 65±11 years) with PD (PD duration: 7±4 years) were eligible to take part in this cross-sectional, exploratory study. The motor symptoms alone explained 36% (F= 17.85, p<0.001) of the variance in the FM scores. When depressive symptoms were included in the model, the explained variance increased to 45% (F= 12.77, p<0.001). This indicated that individuals who had lower motor and depressive symptoms were less likely to have limitations in FM. Conclusion: The findings of the present study demonstrated that motor symptoms were the best potential predictor of FM in individuals with PD, according to mPAS scores. Additionally, the presence of depressive symptoms should not be overlooked.

Mobilidade funcional (MF) é a capacidade das pessoas de se movimentarem em diferentes ambientes, incluindo em casa, no trabalho e na comunidade, a fim de realizar atividades ou tarefas funcionais, de forma independente e segura. Objetivo: Investigar quais variáveis (gravidade das alterações motoras, sintomas depressivos e fadiga) têm maior impacto na MF avaliada por meio da Escala Modificada de Atividade em Parkinson (mPAS) em indivíduos com doença de Parkinson (DP). Método: A MF avaliada por meio da mPAS, que inclui 14 atividades em três domínios (transferências de cadeira, acinesia da marcha, mobilidade na cama). Escala Unificada de Avaliação da Doença de Parkinson (UPDRS) Parte III, Inventário de Depressão de Beck (BDI) e Escala de Fadiga da Doença de Parkinson-16 (PFS-16) foram usados. Resultados: 45 indivíduos (idade: 65 ± 11 anos) com DP (duração do DP: 7 ± 4 anos) participaram deste estudo transversal e exploratório. A gravidade das alterações motoras explicou 36% (F= 17,85, p <0,001) da variância nos escores de MF. Quando os sintomas depressivos foram incluídos no modelo, a variância explicada aumentou para 45% (F= 12,77, p <0,001). Isso indicou que indivíduos com menor gravidade das alterações motoras e sintomas depressivos eram menos propensos a ter limitações na MF. Conclusão: As alterações motoras foram o principal preditor da MF em indivíduos com DP, de acordo com os escores da mPAS. Além disso, a presença de sintomas depressivos não deve ser negligenciada.

Effects of Glutamine and Alanine Supplementation on Adiposity, Plasma Lipid Profile, and Adipokines of Rats Submitted to Resistance Training.

Glutamine and alanine are lipogenic and could prevent the effects of resistance training (RT) in reducing adiposity and modulating lipid profile. Thus, we aimed to investigate the effects of RT and glutamine and alanine supplementation, in their free or conjugated form, on relative epididymal adipose tissue (EAT) and brown adipose tissue (BAT) weight, plasma lipid profile, and adipokines in EAT. Thirty Wistar rats, aged two months, were distributed into five groups: control (CTRL), trained (TRN), trained and supplemented with alanine (ALA), glutamine and alanine in their free form (GLN+ALA), or L-alanyl-L-glutamine (DIP). Trained groups underwent a ladder-climbing exercise for eight weeks, with progressive load increase. Supplementations were offered in a solution with a concentration of 4% in the last 21 days of training. Food consumption and body weight gain were decreased in the TRN group compared with CTRL. RT also reduced relative EAT and BAT weight, while supplementations, especially with ALA, increased adipose tissue mass. RT reduced total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) (TRN vs. CTRL), whereas glutamine and alanine supplementation increased TC and LDL-c, impairing lipid profile modulation by physical exercise. RT did not affect the concentrations of adipokines in EAT, but DIP supplementation increased interleukin- (IL-) 6 and IL-10. In conclusion, RT reduced adiposity and modulated lipid profile, whereas glutamine and alanine supplementation increased adiposity and impaired lipid profile but increased the concentration of the anti-inflammatory cytokines IL-6 and IL-10 in EAT.

Efeito da ingestão de sucos de laranja, variedades Moro e Pera, sobre o estresse oxidativo de camundongos saudáveis e com resistência à insulina induzida por dieta hiperlipídica e hiperglicídica / Effect of orange juices intake, cv. Moro and Pera, in oxidative stress of healthy and insulin resistant mice induced by high-fat and high carbohydrate diet

As laranjas, das variedades Moro e Pera, são conhecidas por sua composição de flavonoides, em especial, a subclasse flavanona, além das antocianinas na laranja Moro. Ambas as subclasses apresentam capacidade antioxidante, anti-inflamatória e hipolipidêmica, podendo atenuar as alterações metabólicas decorrentes do consumo de uma dieta hiperlipídica e hiperglicídica. Assim, o objetivo deste trabalho foi avaliar o efeito da ingestão de sucos de laranja, das variedades Moro e Pera, sobre os parâmetros oxidativos de camundongos saudáveis e com resistência à insulina, esta última induzida por uma dieta hiperlipídica e hiperglicídica. Camundongos machos, da linhagem C57Bl/6, foram distribuídos em seis grupos, três grupos receberam uma dieta controle e três grupos uma dieta hiperlipídica e hiperglicídica, durante 12 semanas. Concomitante às dietas, dois grupos de cada tratamento receberam suco de laranja Pera e o outro suco de laranja Moro em substituição à água de beber. Na 10ª e 11ª semana, foram realizados o ipITT e o ipGTT. No final do tratamento, foram coletados o sangue, fígado e coração. As flavanonas majoritárias caracterizadas em ambos os sucos foram a narirutina e hesperitina. Além das flavanonas, a cianidina 3-glucosídeo foi a antocianina majoritária no suco de laranja Moro. O consumo de dieta hiperlipídica e hiperglicídica acarretou em ganho de peso e adiposidade corporal, além de alterações metabólicas, como intolerância à insulina e a glicose, com o desenvolvimento da resistência insulínica, de acordo com o índice de HOMA-IR. Contudo, o suco de laranja, da variedade Pera, foi capaz de atenuar os parâmetros metabólicos como a sensibilidade à insulina, além da adiposidade e peso corporal. No tecido hepático, foi observado redução da peroxidação lipídica e da expressão proteica da enzima catalase nos animais tratados com dieta hiperlipídica e hiperglicídica, quando comparado à dieta controle; e aumento na atividade de superóxido dismutase no tecido cardíaco. Não se observou diferenças significativas nas demais enzimas antioxidantes, bem como no dano oxidativo ao DNA avaliado pelo ensaio do cometa. No tecido cardíaco, foi observado aumento da peroxidação lipídica e de glutationa peroxidase nos animais tratados com dieta controle mais suco de laranja Pera e suco de laranja Moro, respectivamente. Assim, a dieta hiperlipídica e hiperglicídica não acarretou em estresse oxidativo e, de maneira geral, os sucos não alteraram este quadro. Como conclusão, o suco de laranja Pera, atenuou as alterações metabólicas relacionadas ao metabolismo de carboidratos, mas não alterou os parâmetros de estresse oxidativo

Oranges, Moro and Pera varieties, are known for their composition of flavonoids, especially the subclass flavanone, beyond the anthocyanins in the Moro variety. Both subclasses present antioxidant, anti-inflammatory and hypolipidemic capacities, and may attenuate the metabolic alterations due to the consumption of a hyperlipidemic and hyperglycemic diet. Thus, the objective of this study was to evaluate the effect of orange juice intake, Moro and Pera varieties, on the oxidative parameters of insulin resistant mice induced by a high-fat and high carbohydrate diet. Mice (C57Bl/6 strain) were distributed in six groups: three groups received a control diet and three groups received a high-fat and high carbohydrate diet during 12 weeks. Concomitantly to the diets, two groups of each treatment received Pera and Moro orange juice in replacement of water. The ipITT and ipGTT were done at 11 e 12 week. At the ending of the treatment, blood, liver and heart were collected. The flavanones narirutine and hesperitin were the major flavanones in both juices. In addition, cyanidin 3-glycoside was the major anthocyanin in Moro orange juice. The consumption of high-fat and high carbohydrate diet resulted in weight gain and body adiposity, and metabolic alterations, such as decrease in insulin tolerance and development of insulin resistance, according to the HOMA-IR index. However, orange juice of the Pera variety was able to attenuate metabolic parameters increasing insulin sensitivity and decreasing adiposity and body weight. In hepatic tissue, decrease on lipid peroxidation and protein expression of the catalase were observed in animals treated with high-fat and high carbohydrate diet when compared to the control diet; and an increase activity of the superoxide dismutase in cardiac tissue. No significant differences were observed in the other antioxidant enzymes, as well as in the oxidative DNA damage assessed by the comet assay. In cardiac tissue, lipid peroxidation and glutathione peroxidase were increased in animals treated with control diet plus Pera and Moro orange juice, respectively. Thus, the high-fat and high carbohydrate diet did not promote oxidative stress and, in general, the juices did not alter oxidative parameters. In conclusion, Pera orange juice attenuate the metabolic alterations related to the metabolism of carbohydrates, but not alter oxidative stress parameters

Effects of Glutamine and Alanine Supplementation on Central Fatigue Markers in Rats Submitted to Resistance Training.

Recent evidence suggests that increased brain serotonin synthesis impairs performance in high-intensity intermittent exercise and specific amino acids may modulate this condition, delaying fatigue. This study investigated the effects of glutamine and alanine supplementation on central fatigue markers in rats submitted to resistance training (RT). Wistar rats were distributed in: sedentary (SED), trained (CON), trained and supplemented with alanine (ALA), glutamine and alanine in their free form (G + A), or as dipeptide (DIP). Trained groups underwent a ladder-climbing exercise for eight weeks, with progressive loads. In the last 21 days, supplementations were offered in water with a 4% concentration. Albeit without statistically significance difference, RT decreased liver glycogen, and enhanced the concentrations of plasma glucose, free fatty acids (FFA), hypothalamic serotonin, and ammonia in muscle and the liver. Amino acids affected fatigue parameters depending on the supplementation form. G + A prevented the muscle ammonia increase by RT, whereas ALA and DIP augmented ammonia and glycogen concentrations in muscle. DIP also increased liver ammonia. ALA and G + A reduced plasma FFA, whereas DIP increased this parameter, free tryptophan/total tryptophan ratio, hypothalamic serotonin, and the serotonin/dopamine ratio. The supplementations did not affect physical performance. In conclusion, glutamine and alanine may improve or impair central fatigue markers depending on their supplementation form.

IL-6 serum levels are elevated in Parkinson's disease patients with fatigue compared to patients without fatigue.

To investigate the influence of interleukin-6 (IL-6) and soluble tumor necrosis factor receptors (sTNFR) in fatigued Parkinson's disease (PD) patients. Forty-four PD patients were evaluated, and fatigue was assessed with the Parkinson Fatigue Scale. Logistic regression analysis was used to evaluate the contribution of disease severity scores and cytokine levels on fatigue scores. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of IL-6 in fatigue. Fatigued PD patients had worse cognitive function and depressive symptoms. These patients had worse PD signs and symptoms, displayed more advanced stages of PD, and had greater functional dependence. There was a significant difference in IL-6 serum levels (p=0.026), but there was no difference in sTNFR levels. Total scores on the Unified Parkinson Disease Rating Scale (ß=1.108; p=0.004) and IL-6 levels (ß=12.843; p=0.020) were found to be significant predictors of fatigue scores. A ROC curve revealed that IL-6 concentrations of 1.18pg/ml represented the best cut-off value for detecting fatigue (sensitivity of 0.941 and specificity of 0.704). Fatigued PD patients have poor clinical outcomes and elevated IL-6 serum levels when compared with non-fatigued patients. These results suggest that IL-6 may play a role in the pathophysiology of fatigue in PD.