Effects of exercise modalities on BDNF and IL-1ß content in circulating total extracellular vesicles and particles obtained from aged rats.

There are evidences about the involvement of systemic factors, such as brain-derived neurotrophic factor (BDNF), on functional exercise effects. Although aerobic exercise can impact circulating extracellular vesicles and particles (EVPs) cargo, other exercise modalities were not studied. Taken that BDNF and anti-inflammatory effects have been related to functional outcomes, and BDNF and IL-1ß have been detected in circulating EVPs, our aim was to evaluate circulating total EVPs profile from adult and aged Wistar rats submitted to exercise modalities, namely aerobic, acrobatic, resistance or combined for 20 min, 3 times a week, during 12 weeks. A modality- and age-dependent effect on total EVPs cargo was observed; aerobic exercise induced an augment in BDNF and IL-1ß in EVPs from aged rats, while acrobatic and combined exercise modalities reduced IL-1ß content in EVPs from adult ones. Besides, all exercise modalities attenuated aging-induced CD63 changes in circulating total EVPs; this finding can be involved with reduced mortality rate and improved memory performance previously observed. Changes on EVPs profile, such as increased CD63 levels can be related, at least in part, to an exercise-induced healthier global status. Additionally, aerobic exercise-induced effects on BDNF and IL-1ß levels might indicate additional benefits in aged individuals.

Early life exposure to hypercaloric diet impairs eating behavior during weaning: The role of BDNF signaling and astrocyte marks.

Literature shows that gestational and/or lactational exposure to hypercaloric diets induces long term effects on eating behavior and the involvement of neurochemical mechanisms. We hypothesized that the effects of hypercaloric diets in early development phases can precede an overweight or an obesity status. The aim of the present study was to evaluate the impact of gestational and lactational exposure to cafeteria diet on eating behavior and neurochemical parameters, BDNF signaling, epigenetic and astrocyte marks in the hippocampus and olfactory bulb during the weaning phase. Pregnant female rats were randomized between standard and cafeteria diet, the respective diet was maintained through the lactational period. The framework of feeding pattern, meal, and its microstructure, was observed in postnatal day 20. Exposure to cafeteria diet increased the number of meals, associated with a lower first inter-meal interval and higher consumption in both genders, without any changes in body weight. Diet exposure also reduced the number of grooming, a behavior typically found at the end of meals. Hypercaloric diet exposure reduced BDNF levels in the olfactory bulb and hippocampus from rats of both sexes and increased the content of the TrkB receptor in hippocampi. It was observed an increase in HDAC5 levels, an epigenetic mark. Still, early exposure to the hypercaloric diet reduced hippocampal GFAP and PPARγ levels, without any effect on NeuN content, indicating that alterations in astrocytes can precede those neuronal outcomes. Our results showed that changes in interrelated neurochemical signaling, BDNF, and astrocyte marks, induced by hypercaloric diet in early stages of development may be related to impairment in the temporal distribution of eating pattern and consequent amounts of consumed food during the weaning phase.

Exercise Modalities Improve Aversive Memory and Survival Rate in Aged Rats: Role of Hippocampal Epigenetic Modifications.

We aimed to investigate the effects of aging and different exercise modalities on aversive memory and epigenetic landscapes at brain-derived neurotrophic factor, cFos, and DNA methyltransferase 3 alpha (Bdnf, cFos, and Dnmt3a, respectively) gene promoters in hippocampus of rats. Specifically, active epigenetic histone markers (H3K9ac, H3K4me3, and H4K8ac) and a repressive mark (H3K9me2) were evaluated. Adult and aged male Wistar rats (2 and 22 months old) were subjected to aerobic, acrobatic, resistance, or combined exercise modalities for 20 min, 3 times a week, during 12 weeks. Aging per se altered histone modifications at the promoters of Bdnf, cFos, and Dnmt3a. All exercise modalities improved both survival rate and aversive memory performance in aged animals (n = 7-10). Exercise altered hippocampal epigenetic marks in an age- and modality-dependent manner (n = 4-5). Aerobic and resistance modalities attenuated age-induced effects on hippocampal Bdnf promoter H3K4me3. Besides, exercise modalities which improved memory performance in aged rats were able to modify H3K9ac or H3K4me3 at the cFos promoter, which could increase gene transcription. Our results highlight biological mechanisms which support the efficacy of all tested exercise modalities attenuating memory deficits induced by aging.

Epigenetic marks are modulated by gender and time of the day in the hippocampi of adolescent rats: A preliminary study.

Although the involvement of gender in epigenetic machinery in peripheral tissues during the neonatal period has been suggested, the gender-related epigenetic profile of brain areas during the adolescent period is rarely exploited. Furthermore, the influence of time of day on hippocampal acetylation marks has been demonstrated in young adult and aged rats; however, there are no studies reporting epigenetic changes in the adolescent period. Therefore, this study aimed to investigate the effects of gender on hippocampal DNA methyltransferase 1 content and histone deacetylase (HDAC) activity of adolescent rats at different time points, specifically early morning and afternoon. Both epigenetic markers increased significantly in the hippocampi of female rats compared to the male group, an indicator of reduced transcriptional activity. In addition, HDAC activity during the early morning was higher compared to afternoon groups in both male and female rats, while DNA methyltransferase 1 content was not altered by the time of day. Our findings demonstrate that hippocampal DNA methylation and histone acetylation status can be influenced by gender during the adolescent period, while the time of the day impacts HDAC activity.

Acute exercise and periodized training in different environments affect histone deacetylase activity and interleukin-10 levels in peripheral blood of patients with type 2 diabetes.

AIMS: Our purpose was to investigate the effects of aerobic periodized training in aquatic and land environments on plasma histone deacetylase (HDAC) activity and cytokines levels in peripheral blood of diabetes mellitus type 2 (T2DM) patients. METHODS: The patients underwent 12 weeks of periodized training programs that including walking or running in a swimming pool (aquatic group) or in a track (dry land group). Blood samples were collected immediately before and after both first and last sessions. Plasma cytokine levels and HDAC activity in peripheral blood mononuclear cell (PBMC) was measured. RESULTS: The exercise performed in both environments similarly modulated the evaluated acetylation mark, global HDAC activity. However, a differential profile depending on the evaluated time point was detected, since exercise increased acutely HDAC activity in sedentary and after 12 weeks of training period, while a reduced HDAC activity was observed following periodized training (samples collected before the last session). Additionally, the 12 weeks of periodized exercise in both environments increased IL-10 levels. CONCLUSIONS: Our data support the hypothesis that the modulation of HDAC activity and inflammatory status might be at least partially related to exercise effects on T2DM. The periodized training performed in both aquatic and land environments impacts similarly epigenetic and inflammatory status.

Differential effect of treadmill exercise on histone deacetylase activity in rat striatum at different stages of development.

The study described herein aimed to evaluate the impact of exercise on histone acetylation markers in striatum from Wistar rats at different stages of development. Male Wistar rats were submitted to two different exercise protocols: a single session of treadmill (running 20 min) or a moderate daily exercise protocol (running 20 min for 2 weeks). Striata of rats aged 39 days postnatal (adolescents), 3 months (young adults), and 20 months (aged) were used. The single exercise session induced persistent effects on global HDAC activity only in the adolescent group, given that exercised rats showed decreased HDAC activity 1 and 18 h after training, without effect on histone H4 acetylation levels. However, the moderate daily exercise did not alter any histone acetylation marker in adolescent and mature groups in any time point evaluated after training. In sum, our data suggest that exercise impacts striatal HDAC activity in an age- and protocol-dependent manner. Specifically, this response seems to be more evident during the adolescent period and might suffer a molecular adaptation in response to chronic training.

Treadmill exercise induces selective changes in hippocampal histone acetylation during the aging process in rats.

Physical exercise and the aging process have been shown to induce opposite effects on epigenetic marks, such as histone acetylation. The impact of exercise on hippocampal histone acetylation on specific lysine residues, especially during the aging process, is rarely studied. The aim of this study was to investigate the effect of treadmill exercise (20min/day during 2 weeks) on H3K9, H4K5 and H4K12 acetylation levels in hippocampi of young adult and aged rats. Male Wistar rats aged 3 or 20-21 months were assigned to sedentary and exercise groups. Single-trial step-down inhibitory avoidance conditioning was employed as an aversive memory paradigm. Hippocampal H3K9, H4K5 and H4K12 acetylation was determined by Western blotting. The daily moderate exercise protocol improved the aversive memory performance and increased hipocampal H4K12 acetylation levels in both tested ages. Exercise was also able to increase H3K9 acetylation levels in aged rats. An age-related decline in memory performance was observed, without any effect of the aging process on histone acetylation state. Our data suggest that treadmill exercise can impact hippocampal the histone acetylation profile in an age- and lysine-dependent manner. In addition, higher hippocampal H4K12 acetylation levels at both ages may be related to improvement of aversive memory performance.

Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats.

Some studies have linked age-related beneficial effects of exercise and epigenetic mechanisms. Although, the impact of treadmill exercise on histone acetylation, histone and DNA methylation marks in aged cortices yet remains poorly understood. Considering the role of frontal cortex on brain functions, we investigated the potential of different exercise protocols, single session and daily exercise, to modulate epigenetic marks, namely global H4 acetylation, histone methyltransferase activity (HMT H3K27) and levels of DNA methytransferase (DNMT1 and DNMT3b) in prefrontal cortices from 3 and 21-months aged Wistar rats. The animals were submitted to two treadmill exercise protocols, single session (20min) or daily moderate (20min/day during 14days). The daily exercise protocol induced an increased in histone H4 acetylation levels in prefrontal cortices of 21-months-old rats, without any effects in young adult group. DNMT3b levels were increased in aged cortices of animals submitted to single session of exercise. These results indicate that prefrontal cortex is susceptible to epigenetic changes in a protocol dependent-manner and that H4 acetylation levels and DNMT3b content changes might be linked at least in part to exercise-induced effects on brain functions.

Treadmill exercise alters histone acetylation differently in rats exposed or not exposed to aversive learning context.

Epigenetic modifications have been linked to memory formation after learning context exposure and to exercise effects on memory performance. The aim of this study was to investigate the effect of treadmill exercise (20 min/day during 2 weeks) on H3K14 acetylation and H3S10 phosphorylation levels in the hippocampi of 3-month-old Wistar rats exposed and not exposed to aversive learning context. Male Wistar rats aged 2-3 months were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. Single-trial step-down inhibitory avoidance (IA) conditioning was employed as an aversive memory model. Epigenetic parameters were determined 30 min after the IA test. A decrease in the H3K14 acetylation in the hippocampus 24 h after IA training (30 min after test session) was observed. Exercise reversed the IA effect, and no effect was observed in the non-IA exposed group. Our data support the hypothesis that modulation of H3K14 acetylation levels in the hippocampus might be related, at least in part, to exercise effects on aversive memory.

Avaliação da capacidade funcional de crianças com paralisia cerebral / Evaluation of the functional capacity of children with cerebral palsy

Objetivo descrever a capacidade funcional de crianças com paralisia cerebral que realizavam atendimentos de Fisioterapia e Fisioterapia e Fonoaudiologia. Métodos estudo descritivo, de caráter transversal, composto por 14 crianças com PC do tipo quadriplegia espástica (6 realizavam Fisioterapia e 8 Fisioterapia e Fonoaudiologia). Foram utilizados para avaliação o Inventário de Avaliação Pediátrica de Incapacidade (PEDI) e o Sistema de Classificação da Função Motora Grossa (GMFCS). As associações entre as variáveis categóricas foram analisadas por meio do teste exato de Fisher. Comparações entre médias foram realizadas utilizando-se o teste t de Student. Resultados não se obteve melhora estatisticamente significante nas áreas de autocuidado, mobilidade e função social entre os dois grupos nos domínios de habilidade funcional e assistência ao cuidador. Conclusão as crianças do grupo Fisioterapia tiveram escores funcionais mais elevados que as do grupo Fisioterapia associado à Fonoaudiologia, mas não houve diferença estatisticamente significante entre os grupos. Isso se deu, provavelmente, devido ao reduzido número de participantes, à diversidade de quadros clínicos que a patologia pode apresentar e a possíveis diferenças na intervenção fisioterapêutica realizada nos dois estados, que possuem situações socioeconômicas bem diversas. .

Purpose to describe the functional capacity of children with cerebral palsy who performed the care of Physical Therapy Specialty and Speech, Language and Hearing Sciences. Methods a cross sectional observational study, comprising 14 children with spastic quadriplegic (6 performed Physiotherapy and 8 performed Physiotherapy and Speech therapy). The Pediatric Evaluation of Disability Inventory (PEDI) and the Manual Abilities Classification System (GMFCS) were used to evaluate them. The associations between categorical variables were analyzed using Fisher exact test. Comparisons between means were performed using the Student t test. Results we didn’t obtain statistically significant improvement in the areas of self-care, mobility and social function between the two groups in the fields of functional skills and caregiver assistance. Conclusion the Physiotherapy group of children had higher functional scores than those in the Physiotherapy group associated with Speech Therapy, but there was no statistically significant difference between the groups. This was probably due to the small number of participants, the diversity of clinical presentation and possible differences of Physical Therapy intervention conducted in two states with very different socioeconomic situations. .

Eficácia da eletroestimulação muscular expiratória na tosse de pacientes após acidente vascular encefálico / Effectiveness of electrical stimulation in expiratory muscle on cough of patients after stroke

Indivíduos com sequelas de acidente vascular encefálico (AVE) apresentam como complicação comum a hipotonia de tronco com consequente fraqueza da sua musculatura, em especial, o reto abdominal que é o principal músculo acionado para a tosse. As correntes elétricas têm sido amplamente utilizadas para recrutamento de fibras musculares nas mais diversas patologias. O presente estudo teve como objetivo avaliar a eficácia da eletroestimulação transcutânea de média frequência (ETMF) na força muscular expiratória e tosse de pacientes com sequela de AVE. Trata-se de um estudo quase-experimental (antes e depois) onde foram selecionados 11 indivíduos pós-AVE entre 40 a 65 anos, ambos os sexos e estáveis hemodinamicamente. Os pacientes foram avaliados quanto a parâmetros clínicos e pneumofuncionais (ventilometria, pico de fluxo expiratório (PFE) e manovacuometria) e submetidos ao protocolo, que constava de ETMF no músculo reto abdominal com o aparelho de corrente Russa, frequência portadora de 2.500 Hz modulada a 40 Hz, durante 15 minutos, por 15 sessões. Na avaliação inicial observou-se diminuição da força muscular inspiratória e expiratória (Pimáx; Pemáx) e do PFE quando comparados aos valores de normalidade preditos na literatura. Após a ETMF houve incremento da Pimáx e Pemáx sem significância estatística (p=0,18 e p=0,29) já o PFE teve um acréscimo de 283,73 L/minuto para 347,27 L/minuto (p=0,03). Pode-se observar que a ETMF foi eficaz no incremento dos parâmetros avaliados, com o PFE sendo o de maior impacto e significância estatística, no entanto, mais estudos com populações maiores se fazem necessários para análise dessa nova abordagem terapêutica.

Individuals with sequelae of stroke present as a common complication hypotonia and weakness of trunk muscles, in special the rectus abdominal muscle which is the main muscle activated for cough. The electrical stimulation (ES) is being widely used to fiber recruitment in many muscle groups and pathologies. The present study aimed to evaluate the efficiency of electrical stimulation with median frequencies (ETMF) in expiratory muscles strength and cough in patients with sequels of stroke. It is a quasi-experimental study (before and after) where 11 individuals were selected after stroke between 40 and 65 years, both sexes and hemodynamically stable. Patients were evaluated about clinic and respiratory scores (ventilometer, peak of expiratory flow (PEF) and manometer (MIP and MEP) and submitted to the protocol, which consisted of ETMF in expiratory muscle (abdominals rectus) with the unit of Russian current with 2,500 Hz carrier frequency modulated at 40 Hz for 15 minutes by 15 sessions. In the initial assessment evidenced decreasing in inspiratory and expiratory muscular strength (MIP, MEP) and PEF when compared to predicted values in literature. In the end of ETMF it happened an increase in MIP, MEP without statistical significance (p=0.18 and p=0.29) but the PEF has had an increase of 283.73 L/minute to 347.27 L/minute (p=0.03). It can be seen that the ETMF was effective in the improvement of the parameters evaluated, with PEF being the greatest impact and statistical significance, however further studies with larger populations are necessary to analyze this new therapeutic approach.