Publications by authors named "Ricardo Mario Arida"

110 Publications

Effects of lower extremity constraint-induced movement therapy on gait and balance of chronic hemiparetic patients after stroke: description of a study protocol for a randomized controlled clinical trial.

Trials 2021 Jul 19;22(1):463. Epub 2021 Jul 19.

Neurology/Neuroscience program, Federal University of São Paulo - UNIFESP, Botucatu street, 862 - 5° floor Edifico Ciências Biomédicas, São Paulo, Brazil.

Background: Protocols involving intensive practice have shown positive outcomes. Constraint induced movement therapy (CIT) appears to be one of the best options for better outcomes in upper limb rehabilitation, but we still have little data about lower extremity constraint-induced movement therapy (LE-CIT) and its effects on gait and balance.

Objective: To evaluate the effects of an LE-CIT protocol on gait functionality and balance in chronic hemiparetic patients following a stroke.

Methods: The study adopts a randomized, controlled, single-blinded study design. Forty-two patients, who suffered a stroke, who were in the chronic phase of recovery (>6 months), with gait disability (no community gait), and who were able to walk at least 10 m with or without the advice or support of 1 person, will be randomly allocated to 2 groups: the LE-CIT group or the control group (intensive conventional therapy). People will be excluded if they have speech deficits that render them unable to understand and/or answer properly to evaluation scales and exercises selected for the protocol and/or if they have suffered any clinical event between the screening and the beginning of the protocol. Outcome will be assessed at baseline (T0), immediately after the intervention (T1), and after 6 months (T2). The outcome measures chosen for this trial are as follows: 6-min walk test (6minWT), 10-m walk test (10mWT), timed up and go (TUG), 3-D gait analysis (3DGA), Mini Balance Evaluation Systems Test (Mini-BESTest), and as a secondary measure, Lower Extremity Motor Activity Log will be evaluated (LE-MAL). The participants in both groups will receive 15 consecutive days of daily exercise. The participants in the LE-CIT group will be submitted to this protocol 2.5 h/day for 15 consecutive days. It will include (1) intensive supervised training, (2) use of shaping as strategy for motor training, and (3) application of a transfer package (plus 30 min). The control group will receive conventional physiotherapy for 2.5 h/day over 15 consecutive days (the same period as the CIT intervention). Repeated measures analyses will be made to compare differences and define clinically relevant changes between groups.

Results: Data collection is currently on-going and results are expected in 2021.

Discussion: LE-CIT seems to be a good protocol for inclusion into stroke survivors' rehabilitation as it has all the components needed for positive results, as well as intensity and transference of gains to daily life activities.

Trial Registration: www.ensaiosclinicos.gov.br RBR-467cv6 . Registered on 10 October 2017. "Effects of Lower Extremities - Constraint Induced Therapy on gait and balance function in chronic hemipretic post-stroke patients".
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http://dx.doi.org/10.1186/s13063-021-05424-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287769PMC
July 2021

The Contribution of Physical Exercise to Brain Resilience.

Front Behav Neurosci 2020 20;14:626769. Epub 2021 Jan 20.

Department of Education in Health, Federal University of Sergipe, Sergipe, Brazil.

Increasing attention has been given to understanding resilience to brain diseases, often described as brain or cognitive reserve. Among the protective factors for the development of resilience, physical activity/exercise has been considered to play an important role. Exercise is known to induce many positive effects on the brain. As such, exercise represents an important tool to influence neurodevelopment and shape the adult brain to react to life's challenges. Among many beneficial effects, exercise intervention has been associated with cognitive improvement and stress resilience in humans and animal models. Thus, a growing number of studies have demonstrated that exercise not only recovers or minimizes cognitive deficits by inducing better neuroplasticity and cognitive reserve but also counteracts brain pathology. This is evidenced before disease onset or after it has been established. In this review, we aimed to present encouraging data from current clinical and pre-clinical neuroscience research and discuss the possible biological mechanisms underlying the beneficial effects of physical exercise on resilience. We consider the implication of physical exercise for resilience from brain development to aging and for some neurological diseases. Overall, the literature indicates that brain/cognitive reserve built up by regular exercise in several stages of life, prepares the brain to be more resilient to cognitive impairment and consequently to brain pathology.
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http://dx.doi.org/10.3389/fnbeh.2020.626769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874196PMC
January 2021

Physical exercise and seizure activity.

Biochim Biophys Acta Mol Basis Dis 2021 01 24;1867(1):165979. Epub 2020 Sep 24.

Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address:

Neuroprotective and antiepileptogenic therapies have been extensively investigated for epilepsy prevention and treatment. This review gives an overview of the promising contribution of the ketogenic diet, a complementary treatment, on the intestinal microbiota to reduce seizure susceptibility. Next, the relevance of physical exercise is extensively addressed as a complementary therapy to reduce seizure susceptibility, and thereby impact beneficially on the epilepsy condition. In this context, particular attention is given to the potential risks and benefits of physical exercise, possible precipitant factors related to exercise and proposed mechanisms by which exercise can reduce seizures, and its antiepileptogenic effects. Finally, this review points to emerging evidence of exercise reducing comorbidities from epilepsy and improving the quality of life of people with epilepsy. Based on evidence from current literature, physical or sport activities represent a potential non-pharmacological intervention that can be integrated with conventional therapy for epilepsy.
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http://dx.doi.org/10.1016/j.bbadis.2020.165979DOI Listing
January 2021

Could epilepsy have been the cause of Bruce Lee's death?: "The athlete and myth of martial arts".

Epilepsy Behav 2020 10 18;111:107310. Epub 2020 Jul 18.

Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

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http://dx.doi.org/10.1016/j.yebeh.2020.107310DOI Listing
October 2020

CoVID-19 vs. epilepsy: It is time to move, act, and encourage physical exercise.

Epilepsy Behav 2020 09 3;110:107154. Epub 2020 May 3.

Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

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http://dx.doi.org/10.1016/j.yebeh.2020.107154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196429PMC
September 2020

Enriched environment and exercise effects on parvalbumin expression and distribution in the hippocampal formation of developing rats.

Brain Res Bull 2020 07 17;160:85-90. Epub 2020 Apr 17.

Faculdade do Clube Náutico Mogiano (FCNM), Mogi das Cruzes, SP, Brazil; Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil; Hospital do Câncer de Muriaé, Fundação Cristiano Varella (FCV), Muriaé, MG, Brazil; Centro Universitário UNIFAMINAS, Muriaé, MG, Brazil. Electronic address:

Several models of environmental enrichment and physical exercise have been used to explore the experience effects on brain functions and plasticity, mainly in adult animals. In order to examine the early influence of these stimuli on developing brain, the present study used calcium-binding protein parvalbumin as neuroplastic marker in the hippocampal formation of male Wistar rats subjected to environmental enrichment or physical exercise from postnatal days 21 to 60 (P21-P60). In our study, no significant difference in hippocampal expression and distribution of parvalbumin was found between enriched and control rats. However, a significant increase in parvalbumin protein expression as well as in the number of neurons stained with parvalbumin was observed in the hippocampal formation of rats submitted to daily treadmill exercise when compared to the control rats. The hippocampal region with the highest number of parvalbumin neurons in exercised rats was Cornus of Amon 2 e 3 (CA2/CA3). These findings indicate that developing brain may be differentially sensitive to environmental stimulation models. Specifically, our results show that hippocampal expression and distribution of parvalbumin in developing rats may be more influenced by exercise than by enriched environment. The mechanisms are not yet known.
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http://dx.doi.org/10.1016/j.brainresbull.2020.03.021DOI Listing
July 2020

Dance promotes positive benefits for negative symptoms in autism spectrum disorder (ASD): A systematic review.

Complement Ther Med 2020 Mar 7;49:102299. Epub 2020 Jan 7.

Department of Education in Health, Federal University of Sergipe, Brazil. Electronic address:

Background: Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder with stereotyped and repetitive behaviors. Dance practice can elicit esthesia to stimulate the communication process through the notion of the phenomenal body that is recognized in an expressive and symbolic space.

Objective: To conduct a systematic review to identify how dance promotes positive benefits for the negative symptoms in ASD.

Method: We formulated the research question based on PICO: "What is the influence of dance on negative symptoms in individuals with autism spectrum disorder?". Databases were searched in March 2019 and included PubMed, Science Direct, Scopus, PsycInfo and Web of Science.

Results: We identified 9,350 studies of which five were selected for our review (a total of 266 individuals). All included studies showed an influence of dance on negative symptoms, including empathy, emotional expression, body awareness, behavior, and psychological wellbeing that impact on social reciprocity, and consequently the communication process, in ASD.

Conclusions: Dance practice may contribute to body awareness and social involvement using techniques that provide mirroring, synchronization, rhythm, and reciprocity in adults with normal to high-functioning ASD.
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http://dx.doi.org/10.1016/j.ctim.2020.102299DOI Listing
March 2020

Resistance Exercise Decreases Amyloid Load and Modulates Inflammatory Responses in the APP/PS1 Mouse Model for Alzheimer's Disease.

J Alzheimers Dis 2020 ;73(4):1525-1539

Laboratório de Neurofisiologia, Depto. Fisiologia - Universidade Federal de São Paulo (UNIFESP/SP), São Paulo, Brazil.

Neuroinflammation has been shown to play a crucial role in the development of Alzheimer's disease (AD) and also has an association with amyloid-β (Aβ) plaques, a hallmark of this disease. Physical exercise has emerged as an alternative treatment for pathological impairment in AD. In light of this evidence, together with the fact that the hippocampus is one of the first structures to be affected in AD, we analyzed hippocampal changes in Aβ load, inflammatory responses, and locomotor activity in transgenic APP/PS1 mouse model for AD submitted to a resistance exercise (RE) program. One month after the start of the RE program, the locomotor hyperactivity related to AD behavior was reduced and microglia recruitment was increased, which in turn may have contributed to the decrease in the volume of Aβ plaques. In addition, the RE program restored the levels of IL-1α, IL-4, and IL-6 cytokines to control levels. Our study indicates that RE has beneficial effects on the locomotor behavior, amyloid burden, and inflammation of AD pathology and can therefore be used as a therapy to improve the clinical symptoms and neurophysiological alterations in AD. To the best of our knowledge, this is the first study to use a resistance exercise program in transgenic AD model.
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http://dx.doi.org/10.3233/JAD-190729DOI Listing
May 2021

Reduction in seizure frequency with a high-intensity fitness program (CrossFit): A case report.

Epilepsy Behav Rep 2020 20;13:100354. Epub 2019 Dec 20.

Department of Physiology-Laboratory of Neurophysiology, Universidade de São Paulo (UNIFESP), Rua Botucatu, 862. Ed. Leal Prado, São Paulo 040023-900, Brazil.

Few studies have reported the impact of intensive exercise on seizure susceptibility. Here, we present a case in which a patient developed drug-resistant focal epilepsy after craniotomy for a low-grade glioma. She had a marked reduction in seizure frequency after switching from moderate exercise to a high-intensity exercise program. Psychological benefits of exhaustive exercise included decreased suicide ideation, in part mediated by fewer seizures.
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http://dx.doi.org/10.1016/j.ebr.2019.100354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950769PMC
December 2019

Early exercise induces long-lasting morphological changes in cortical and hippocampal neurons throughout of a sedentary period of rats.

Sci Rep 2019 09 23;9(1):13684. Epub 2019 Sep 23.

Research and Technology Center, University of Mogi das Cruzes, Mogi das Cruzes, SP, Brazil.

Life experiences at early ages, such as physical activity in childhood and adolescence, can result in long-lasting brain effects able to reduce future risk of brain disorders and to enhance lifelong brain functions. However, how early physical exercise promotes these effects remains unclear. A possible hypothesis is that physical exercise increases the expression of neurotrophic factors and stimulates neuronal growth, resulting in a neural reserve to be used at later ages. Basing our study on this hypothesis, we evaluated the absolute number and morphology of neuronal cells, as well as the expression of growth, proliferation and survival proteins (BDNF, Akt, mTOR, p70S6K, ERK and CREB) in the cerebral cortex and hippocampal formation throughout of a sedentary period of rats who were physically active during youth. To do this, male Wistar rats were submitted to an aerobic exercise protocol from the 21 to the 60 postnatal days (P21-P60), and evaluated at 0 (P60), 30 (P90) and 60 (P120) days after the last exercise session. Results showed that juvenile exercise increased, and maintained elevated, the number of cortical and hippocampal neuronal cells and dendritic arborization, when evaluated at the above post-exercise ages. Hippocampal BDNF levels and cortical mTOR expression were found to be increased at P60, but were restored to control levels at P90 and P120. Overall, these findings indicate that, despite the short-term effects on growth and survival proteins, early exercise induces long-lasting morphological changes in cortical and hippocampal neurons even during a sedentary period of rats.
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http://dx.doi.org/10.1038/s41598-019-50218-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757043PMC
September 2019

Physical exercise during pregnancy minimizes PTZ-induced behavioral manifestations in prenatally stressed offspring.

Dev Psychobiol 2020 03 20;62(2):240-249. Epub 2019 Sep 20.

Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

Stress during gestation has been shown to affect susceptibility and intensity of seizures in offspring. Environmental stimuli, such as maternal physical exercise, have shown to be beneficial for brain development. Although studies have demonstrated the deleterious influence of stress during pregnancy on seizure manifestation in offspring, very little is known on how to minimize these effects. This study verified whether physical exercise during the pregnancy associated with prenatal stress minimizes seizure susceptibility in offspring at the beginning of postnatal development. Pregnant rats and male pups were divided into the following groups: control, stress, stress/forced exercise, and stress/voluntary exercise. Behavioral manifestations were analyzed after injection of pentylenetetrazol (PTZ; 45 and 60 mg/kg) at ages P15 and P25. Increased behavioral manifestations and seizure severity was observed in the stress group compared with the control group at both ages. At the dose of 45 mg/kg, offspring of stressed mothers who performed both physical exercise models showed an increase in latency for the first manifestation and decrease in the seizures severity at both ages compared with the mothers groups who were only stressed. Prenatal restraint stress potentiated PTZ-induced seizure behavior, and both forced and voluntary exercise during gestation attenuates the negative effects of PTZ-induced offspring.
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http://dx.doi.org/10.1002/dev.21895DOI Listing
March 2020

Dance for neuroplasticity: A descriptive systematic review.

Neurosci Biobehav Rev 2019 01 10;96:232-240. Epub 2018 Dec 10.

Department of Psychiatry, Federal University of São Paulo, 341 Major Maragliano Street, Vila Mariana, CEP: 04017-030, São Paulo, Brazil. Electronic address:

We conducted a systematic review of randomized clinical trials to investigate whether dance practice promotes neuroplasticity. We also determined how dancing is able to alter (1) brain volumes and structures (2) brain function, (3) psychomotor adjustment and (4) levels of neurotrophic factors. This systematic review formulated a research question based on PICO, according to the guidelines for systematic reviews and meta-analyzes (PRISMA), "What is the influence of dance practice on neuroplasticity in already mature brains?" We screened 1071 studies and from these eight studies were included in the review. Of the selected studies, all demonstrated positive structural and/or functional changes. Structural changes included increased hippocampal volume, gray matter volume in the left precentral and parahippocampal gyrus, and white matter integrity. Functional changes included alterations in cognitive function such as significant improvement in memory, attention, body balance, psychosocial parameters and altered peripheral neurotrophic factor. Based on the evidence, dance practice integrates brain areas to improve neuroplasticity.
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http://dx.doi.org/10.1016/j.neubiorev.2018.12.010DOI Listing
January 2019

Hippocampal distribution of parvalbumin neurons in female and male rats submitted to the same volume and intensity of aerobic exercise.

Neurosci Lett 2019 01 15;690:162-166. Epub 2018 Oct 15.

Hospital Israelita Albert Einstein (HIAE), São Paulo, SP, Brazil; Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil. Electronic address:

Several studies report the influence of gender on physical exercise-induced brain plasticity, including neurotrophic factor levels, neurogenesis, and navigation strategies in spatial memory task. However, it has been noted that females are physically more active than males in animal models of physical exercise. With this in mind, we conducted an experimental study to investigate the effect of sex on the brain of rats submitted to same volume and intensity of aerobic exercise. To do so, we used calcium-binding protein parvalbumin as neuroplastic marker to explore the hippocampal formation (a brain neurogenic/mnemonic region) of male and female rats submitted to 4 weeks of aerobic exercise on a treadmill at 12 m/min, 30 min per day. Our results show that, in both sexes, physical exercise increased hippocampal density of parvalbumin neurons in the cornus ammonis (CA1, CA2/3) and hilus subfields, but not in the dentate gyrus and subiculum. No difference in exercise-induced hipocampal parvalbumin density was found between male and female rats. These findings suggest that aerobic exercise promotes similar effects on hippocampal distribution of parvalbumin neurons of male and female rats, especially when they are submitted to the same volume and intensity of physical exercise.
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http://dx.doi.org/10.1016/j.neulet.2018.10.028DOI Listing
January 2019

Cortical and hippocampal expression of inflammatory and intracellular signaling proteins in aged rats submitted to aerobic and resistance physical training.

Exp Gerontol 2018 09 26;110:284-290. Epub 2018 Jun 26.

Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil. Electronic address:

Aging is often accompanied by an increase in pro-inflammatory markers. This inflammatory process is directly related to cellular dysfunctions that induce events such as the exacerbated activation of cell death signaling pathways. In the aged brain, dysregulation of the normal activities of neuronal cells compromises brain functions, thereby favoring the onset of neurodegenerative diseases and cognitive deficits. Interactions between various stimuli, such as stress, are responsible for the modulation of cellular processes and activities. Physical exercise is a controllable model of stress, largely used as a strategy for studying the physiological mechanisms of inflammatory responses and their consequences. However, different types of physical exercise promote different responses in the organism. The present study was designed to investigate the expression of inflammatory cytokines and chemokines, and expression and activation of intracellular signaling proteins (CREB, ERK, Akt, p70S6k, STAT5, JNK, NFkB e p38) in the cerebral cortex and hippocampal formation of aged rats submitted to aerobic and resistance exercise. Inflammatory analysis showed that aged rats that underwent resistance training had decreased cortical levels of RANTES and a reduction in the hippocampal levels of MIP-2 when compared with control animals (sedentary). No significant difference was detected in the cortical and hippocampal inflammatory response between aerobic and sedentary groups. However, when comparing the two training models (aerobic vs resistance), it was observed that aerobic training increased the cortical levels of IL-13, IL-6, IL-17α compared with resistance training. Regarding the signaling proteins, a significant increase in cortical expression of the proteins JNK, ERK and p70S6k was found in the aerobic group in relation to the sedentary group. No significant change in the cortical and hippocampal expression of signaling proteins was detected between resistance training and sedentary groups. Nevertheless, when training models were compared, it was observed that aerobic training increased cortical expression of the total proteins p38, ERK, Akt and p70S6k in relation to resistance training. Taken together, these results show that changes in the brain expression of inflammatory and cell survival proteins in aged rats depend on the type of physical training.
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http://dx.doi.org/10.1016/j.exger.2018.06.025DOI Listing
September 2018

Hippocampal microRNA-mRNA regulatory network is affected by physical exercise.

Biochim Biophys Acta Gen Subj 2018 08 8;1862(8):1711-1720. Epub 2018 May 8.

Department of Physiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address:

Background: It is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs.

Methods: To verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise. Cognition was evaluated by a multiple trial inhibitory avoidance (MTIA) task and Illumina next-generation sequencing (NGS) was used for miRNA and mRNA profiling.

Results: Exercise improved memory retention but not acquisition in the MTIA task. It was observed that 4 miRNAs and 54 mRNAs were significantly altered in the hippocampus of Ex2 (euthanized 2 h after the last exercise bout) group when compared to CTL group. Bioinformatic analysis showed an inverse correlation between 3 miRNAs and 6 target mRNAs. The miRNAs miR-129-1-3p and miR-144-5p were inversely correlated to the Igfbp5 and Itm2a, respectively, and the miR-708-5p presented an inverse correlation with Cdkn1a, Per2, Rt1-a2.

Conclusion: The exercise-induced memory improvements are accompanied by changes in hippocampal miRNA-mRNA regulatory network.

General Significance: Physical exercise can affect brain function through modulation of epigenetics mechanisms involving miRNA regulation.
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http://dx.doi.org/10.1016/j.bbagen.2018.05.004DOI Listing
August 2018

A Comparative Study of Conventional Physiotherapy versus Robot-Assisted Gait Training Associated to Physiotherapy in Individuals with Ataxia after Stroke.

Behav Neurol 2018 20;2018:2892065. Epub 2018 Feb 20.

Physiology Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.

Objectives: To assess the influence of RAGT on balance, coordination, and functional independence in activities of daily living of chronic stroke survivors with ataxia at least one year of injury.

Methods: It was a randomized controlled trial. The patients were allocated to either therapist-assisted gait training (TAGT) or robotic-assisted gait training (RAGT). Both groups received 3 weekly sessions of physiotherapy with an estimated duration of 60 minutes each and prescribed home exercises. The following outcome measures were evaluated prior to and after the completion of the 5-month protocol treatment: BBS, TUG test, FIM, and SARA. For intragroup comparisons, the Wilcoxon test was used, and the Mann-Whitney test was used for between-group comparison.

Results: Nineteen stroke survivors with ataxia sequel after one year of injury were recruited. Both groups showed statistically significant improvement ( < 0.05) in balance, functional independencein, and general ataxia symptoms. There were no statistically significant differences ( < 0.05) for between-group comparisons both at baseline and after completion of the protocol.

Conclusions: Chronic stroke patients with ataxia had significant improvements in balance and independence in activities of daily living after RAGT along with conventional therapy and home exercises. This trial was registered with trial registration number 39862414.6.0000.5505.
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http://dx.doi.org/10.1155/2018/2892065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838477PMC
September 2018

Physical exercise alters the activation of downstream proteins related to BDNF-TrkB signaling in male Wistar rats with epilepsy.

J Neurosci Res 2018 05 2;96(5):911-920. Epub 2017 Nov 2.

Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, Brazil.

There are a considerable number of studies concerning the behavioral effects of physical exercise on the epileptic brain; however, the intracellular signaling mechanisms involved remain unclear. We investigated the effects of aerobic exercise on hippocampal levels of brain-derived neurotrophic factor (BDNF), expression of its receptor tropomyosin receptor kinase B (TrkB), and activation of intracellular proteins related to BDNF-TrkB signaling in male Wistar rats with pilocarpine-induced epilepsy. Thirty days after the first spontaneous seizure, rats from the exercise group undertook a 30-day physical exercise program on the treadmill. Thereafter, BDNF levels, expression of TrkB, and activation of intracellular proteins were quantified by enzyme-linked immunosorbent assay, Western blotting, and multiplex assay, respectively. Statistical analyses were conducted using nonparametric tests. Rats with epilepsy presented decreased BDNF levels compared with control rats. BDNF levels increased significantly in the exercise group compared with the epileptic and control groups. Expression of full-length and truncated TrkB was increased in rats with epilepsy, and physical exercise restored its expression to control levels. RAC-alpha serine/threonine-protein kinase, mammalian target of rapamycin, and extracellular signal-regulated kinase activation were reduced in rats with epilepsy, and exercise increased activation compared with control and epilepsy groups. Increased cAMP response element binding protein activation was observed in the exercise group compared with the epilepsy group. Our findings indicate that the beneficial effects of exercise in the epileptic brain can be in part related to alterations in the activation of proteins related to the BDNF-TrkB signaling pathway.
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http://dx.doi.org/10.1002/jnr.24196DOI Listing
May 2018

Aerobic exercise in adolescence results in an increase of neuronal and non-neuronal cells and in mTOR overexpression in the cerebral cortex of rats.

Neuroscience 2017 Oct 9;361:108-115. Epub 2017 Aug 9.

Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil; Hospital Israelita Albert Einstein (HIAE), São Paulo, SP, Brazil. Electronic address:

Better cognitive performance and greater cortical and hippocampal volume have been observed in individuals who undertook aerobic exercise during childhood and adolescence. One possible explanation for these beneficial effects is that juvenile physical exercise enables better neural development and hence more cells and neuronal circuitries. It is probable that such effects occur through intracellular signaling proteins associated with cell growth, proliferation and survival. Based on this information, we evaluated the number of neuronal and non-neuronal cells using isotropic fractionation and the expression and activation of intracellular proteins (ERK, CREB, Akt, mTOR and p70S6K) in the cerebral cortex and hippocampal formation of the rats submitted to a physical exercise program on a treadmill during adolescence. Results showed that physical exercise increases the number of neuronal and non-neuronal cortical cells and hippocampal neuronal cells in adolescent rats. Moreover, mTOR overexpression was found in the cortical region of exercised adolescent rats. These findings indicate a significant cellular proliferative effect of aerobic exercise on the cerebral cortex in postnatal development.
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http://dx.doi.org/10.1016/j.neuroscience.2017.08.002DOI Listing
October 2017

Effects of acute physical exercise in the light phase of sleep in rats with temporal lobe epilepsy.

Epilepsy Res 2017 10 21;136:54-61. Epub 2017 Jul 21.

Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil. Electronic address:

Objective: Our aim was to investigate the influence of an acute exercise session on sleep pattern in rats with temporal lobe epilepsy (TLE).

Methods: Twenty male Wistar rats were randomly assigned to 4 groups: control (C); acute exercise (EX); epilepsy (E) and epilepsy acute exercise (EEX). Two sleep electrocorticography recordings were performed during the light phase [baseline and day 2 (after the acute physical exercise session)]. After baseline recording, the exercise groups (EX and EEX) were submitted to an exercise session on a motor-driven treadmill at 12m/min for 30min. Twelve hours later, the rats were submitted to the second sleep recording.

Results: At baseline, the E group showed a higher wakefulness and a lower Total sleep time, Slow Wave Sleep and REM sleep compared with the C group. After acute exercise, there was an increase in Total sleep time and Slow Wave Sleep and a decrease of wakefulness in EEX (+11.10%, +20.29% and -11.25%, respectively) and EX (+5.20%, +11.60% and -8.12%, respectively) groups.

Conclusion: These findings suggest that acute physical exercise positively impacts the sleep pattern of rats with TLE, inducing a more consolidated sleep.
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http://dx.doi.org/10.1016/j.eplepsyres.2017.07.012DOI Listing
October 2017

Physical exercise as an epigenetic modulator of brain plasticity and cognition.

Neurosci Biobehav Rev 2017 Sep 27;80:443-456. Epub 2017 Jun 27.

Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA; Department of Neurosurgery, UCLA Brain Injury Research Center, University of California, Los Angeles, CA 90095, USA. Electronic address:

A large amount of evidence has demonstrated the power of exercise to support cognitive function, the effects of which can last for considerable time. An emerging line of scientific evidence indicates that the effects of exercise are longer lasting than previously thought up to the point to affect future generations. The action of exercise on epigenetic regulation of gene expression seem central to building an "epigenetic memory" to influence long-term brain function and behavior. In this review article, we discuss new developments in the epigenetic field connecting exercise with changes in cognitive function, including DNA methylation, histone modifications and microRNAs (miRNAs). The understanding of how exercise promotes long-term cognitive effects is crucial for directing the power of exercise to reduce the burden of neurological and psychiatric disorders.
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http://dx.doi.org/10.1016/j.neubiorev.2017.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705447PMC
September 2017

Aerobic exercise reduces hippocampal ERK and p38 activation and improves memory of middle-aged rats.

Hippocampus 2017 08 1;27(8):899-905. Epub 2017 Jun 1.

Universidade de Mogi das Cruzes (UMC). Mogi das Cruzes - SP, Brazil.

Aging is often accompanied by cognitive decline, memory impairment, and an increased susceptibility to neurodegenerative disorders. Although the physiological processes of aging are not fully understood, these age-related changes have been interpreted by means of various cellular and molecular theories. Among these theories, alterations in the intracellular signaling pathways associated with cell growth, proliferation, and survival have been highlighted. Based on these observations and on recent evidence showing the beneficial effects of exercise on cognitive function in the elderly, we investigated the cell signaling pathways in the hippocampal formation of middle-aged rats (18 months old) submitted to treadmill exercise over 10 days. To do this, we evaluated the hippocampal activation of intracellular signaling proteins linked to cell growth, proliferation, and survival, such as Akt, mTOR, p70S6K, ERK, CREB, and p38. We also explored the cognitive performance (inhibitory avoidance) of middle-aged rats. It was found that physical exercise reduces ERK and p38 activation in the hippocampal formation of aged rats, when compared to the control group. The hippocampal activation and expression of Akt, mTOR, p70S6K, and CREB were not statistically different between the groups. It was also observed that aged rats from the exercise group exhibited better cognitive performance in the inhibitory avoidance task (aversive memory) than aged rats from the control group. Our results indicate that physical exercise reduces intracellular signaling pathways linked to inflammation and cell death (i.e., ERK and p38) and improves memory in middle-aged rats.
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http://dx.doi.org/10.1002/hipo.22740DOI Listing
August 2017

Resistance Exercise Reduces Seizure Occurrence, Attenuates Memory Deficits and Restores BDNF Signaling in Rats with Chronic Epilepsy.

Neurochem Res 2017 Apr 11;42(4):1230-1239. Epub 2017 Jan 11.

Departamento de Fisiologia, Universidade Federal de São Paulo, Rua Botucatu 862, Ed. Ciências Biomédicas, 5° andar. Vila Clementino, São Paulo, SP, 04023-900, Brazil.

Epilepsy is a disease characterized by recurrent, unprovoked seizures. Cognitive impairment is an important comorbidity of chronic epilepsy. Human and animal model studies of epilepsy have shown that aerobic exercise induces beneficial structural and functional changes and reduces the number of seizures. However, little is yet understood about the effects of resistance exercise on epilepsy. We evaluated the effects of a resistance exercise program on the number of seizures, long-term memory and expression/activation of signaling proteins in rats with epilepsy. The number of seizures was quantified by video-monitoring and long-term memory was assessed by an inhibitory avoidance test. Using western blotting, multiplex and enzyme-linked immunosorbent assays, we determined the effects of a 4-week resistance exercise program on IGF-1 and BDNF levels and ERK, CREB, mTOR activation in the hippocampus of rats with epilepsy. Rats with epilepsy submitted to resistance exercise showed a decrease in the number of seizures compared to non-exercised epileptic rats. Memory deficits were attenuated by resistance exercise. Rats with epilepsy showed an increase in IGF-1 levels which were restored to control levels by resistance exercise. BDNF levels and ERK and mTOR activation were decreased in rats with epilepsy and resistance exercise restored these to control levels. In conclusion, resistance exercise reduced seizure occurrence and mitigated memory deficits in rats with epilepsy. These resistance exercise-induced beneficial effects can be related to changes in IGF-1 and BDNF levels and its signaling protein activation. Our findings indicate that the resistance exercise might be included as complementary therapeutic strategy for epilepsy treatment.
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http://dx.doi.org/10.1007/s11064-016-2165-9DOI Listing
April 2017

Epilepsy and exercise: An experimental study in female rats.

Physiol Behav 2017 03 6;171:120-126. Epub 2017 Jan 6.

Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address:

Objective: Epilepsy is the most common neurological chronic condition worldwide, affecting about 2% of world population. Temporal lobe epilepsy (TLE) reaches 40% of all cases of this condition, and it is highly refractory to pharmacological treatment. Physical activity has been suggested as complementary therapy for epilepsy. However, there is no consistent information whether all these effects are plenty applicable to females, since clinical and experimental studies concerning physical exercise and epilepsy are largely performed in males. Females are worthy of special attention due to gender specific particularities such as hormonal cyclical rhythm and possible pregnancy. Therefore, this study aimed to investigate the impact of two types of exercise programs (Forced and Voluntary) in female Wistar rats submitted to temporal lobe epilepsy induced by pilocarpine.

Methods: Animals were divided into four groups: Control (healthy), Epilepsy, Epilepsy/Forced (exercise in a treadmill) and Epilepsy/Voluntary (free access to wheel). Behavioral and histological analyses were evaluated among groups.

Results: Voluntary exercise was able to reduce seizure frequency and anovulatory estrous cycle occurrence. Yet, both types of exercise attenuated the mossy fiber sprouting in dentate gyrus.

Conclusion: Our results indicate that voluntary exercise exerts a positive effect on epilepsy in female gender. Further investigations are necessary to better elucidate mechanisms involved in these responses, since these effects do not act in the same manner in male and female rats.
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http://dx.doi.org/10.1016/j.physbeh.2016.12.040DOI Listing
March 2017

Does resistance exercise exert a role in hippocampal neurogenesis?

J Physiol 2016 11;594(22):6799

Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu 862, Ed. Ciências Biomédicas, 5°andar. Vila Clementino, CEP 04023-900, São Paulo, SP, Brazil.

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http://dx.doi.org/10.1113/JP272309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108914PMC
November 2016

Effects of different physical exercise programs on susceptibility to pilocarpine-induced seizures in female rats.

Epilepsy Behav 2016 11 22;64(Pt A):262-267. Epub 2016 Oct 22.

Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo, - SP, Brazil. Electronic address:

In epilepsy, the most common serious neurological disorder worldwide, several investigations in both humans and animals have shown the effectiveness of physical exercise programs as a complementary therapy. Among the benefits demonstrated, regular exercise can decrease the number of seizures as well as improve cardiovascular and psychological health in people with epilepsy. While many studies in animals have been performed to show the beneficial effects of exercise, they exclusively used male animals. However, females are also worthy of investigation because of their cyclical hormonal fluctuations and possible pregnancy. Considering the few animal studies concerning seizure susceptibility and exercise programs in females, this study aimed to verify whether exercise programs can interfere with seizure susceptibility induced by pilocarpine in adult female Wistar rats. Animals were randomly divided into three groups: control, forced, and voluntary (animals kept in a cage with a wheel). After the final exercise session, animals received a pilocarpine hydrochloride (350 mg/kg i.p.; Sigma) injection to induce seizures. To measure the intensity of pilocarpine-induced motor signs, we used a scale similar to that developed by Racine (1972) in the kindling model. During a 4-h period of observation, we recorded latency for first motor signs, latency for reaching SE, number of animals that developed SE, and intensity of pilocarpine-induced motor signs. No difference was observed among groups in latency for first motor signs and in the number of animals that developed SE. Although the voluntary group presented more intense motor signs, an increased latency for developing SE was observed compared with that in forced and control groups. Our behavioral results are not enough to explain physiological and molecular pathways, but there are mechanisms described in literature which may allow us to propose possible explanations. Voluntary exercise increased latency to SE development. Further investigation is necessary to elucidate the pathways involved in these results, while more studies should be performed regarding gender specific differences.
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http://dx.doi.org/10.1016/j.yebeh.2016.08.011DOI Listing
November 2016

The Spiritism as therapy in the health care in the epilepsy.

Rev Bras Enferm 2016 Jul-Aug;69(4):804-10

Universidade Federal de São Paulo, Department of Physiology. São Paulo, Brazil.

Objective: to present a brief history of Spiritism, the vision of epilepsy by Spiritism, and the potential of spirituality and religiosity care as complementary and coadjutants treatments in epilepsy.

Method: this is a brief review about the impact of faith, spirituality, and religiosity, particularly the Spiritism philosophy as complementary treatment to neurological disorders (particularly focusing on epilepsy) and mental health. We conduct a review of published articles (about religion/spirituality and epilepsy) in the Pubmed and SciELO databases.

Conclusion: the exercise of spirituality and religiosity can be a positive coping strategy to support the traditional therapy of patients with epilepsy and other neurological disorders. However, it is necessary to demystify myths and beliefs about the epilepsy and improve knowledge about this important health dimension among professionals, patients, and caregivers to explore their full treatment and supportive potential.
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http://dx.doi.org/10.1590/0034-7167.2016690425iDOI Listing
October 2017

Omega-3 Fatty Acids: Possible Neuroprotective Mechanisms in the Model of Global Ischemia in Rats.

J Nutr Metab 2016 24;2016:6462120. Epub 2016 May 24.

Faculty of Medicine, Estácio of Juazeiro do Norte (FMJ), Rua Tenente Raimundo Rocha 515, 63040-360 Juazeiro do Norte, CE, Brazil; Federal University of Ceará (UFC), Rua Coronel Nunes de Melo 1127, 60430-270 Fortaleza, CE, Brazil.

Background. Omega-3 (ω3) administration was shown to protect against hypoxic-ischemic injury. The objectives were to study the neuroprotective effects of ω3, in a model of global ischemia. Methods. Male Wistar rats were subjected to carotid occlusion (30 min), followed by reperfusion. The groups were SO, untreated ischemic and ischemic treated rats with ω3 (5 and 10 mg/kg, 7 days). The SO and untreated ischemic animals were orally treated with 1% cremophor and, 1 h after the last administration, they were behaviorally tested and euthanized for neurochemical (DA, DOPAC, and NE determinations), histological (Fluoro jade staining), and immunohistochemical (TNF-alpha, COX-2 and iNOS) evaluations. The data were analyzed by ANOVA and Newman-Keuls as the post hoc test. Results. Ischemia increased the locomotor activity and rearing behavior that were partly reversed by ω3. Ischemia decreased striatal DA and DOPAC contents and increased NE contents, effects reversed by ω3. This drug protected hippocampal neuron degeneration, as observed by Fluoro-Jade staining, and the increased immunostainings for TNF-alpha, COX-2, and iNOS were partly or totally blocked by ω3. Conclusion. This study showed a neuroprotective effect of ω3, in great part due to its anti-inflammatory properties, stimulating translational studies focusing on its use in clinic for stroke managing.
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http://dx.doi.org/10.1155/2016/6462120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895039PMC
June 2016

A single bout of resistance exercise improves memory consolidation and increases the expression of synaptic proteins in the hippocampus.

Hippocampus 2016 08 7;26(8):1096-103. Epub 2016 Apr 7.

Department of Physiology, Universidade Federal De São Paulo (UNIFESP), São Paulo, Brazil.

Over the past decade, several studies have indicated that chronic resistance exercise (i.e., strength training, weight lifting, etc.) is beneficial for brain health and cognitive function. However, little is known about the effects of a single bout of resistance exercise on brain function, particularly on memory consolidation. Therefore, the purpose of the present study is to examine the effects of a single bout of resistance exercise applied immediately after the training of fear conditioning on memory consolidation and on the expression of IGF-1 and synaptic proteins in the hippocampus. Male Wistar rats were familiarized with climbing a ladder without a load for 3 days and randomly assigned into control (CTL) and resistance exercise (RES) groups. The RES group was subjected to a single bout of resistance exercise applied immediately after fear conditioning training. Subsequently, the animals were tested for contextual (24 h) and tone (48 h) fear memory. Another group of animals were subjected to a single bout of resistance exercise and euthanized 24 h later for hippocampal analysis of IGF-1 and synaptic proteins (synapsin I, synaptophysin, and PSD-95). The exercised rats improved contextual but not tone fear memory. Hippocampal IGF-1 was not altered by resistance exercise. However, the levels of synapsin I, synaptophysin, and PSD-95 increased significantly in the RES group. The results suggested that a single bout of resistance exercise applied immediately after fear conditioning could improve contextual memory, probably through the activation of pre- and postsynaptic machinery required for memory consolidation. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/hipo.22590DOI Listing
August 2016

Maternal Exercise during Pregnancy Increases BDNF Levels and Cell Numbers in the Hippocampal Formation but Not in the Cerebral Cortex of Adult Rat Offspring.

PLoS One 2016 15;11(1):e0147200. Epub 2016 Jan 15.

Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.

Clinical evidence has shown that physical exercise during pregnancy may alter brain development and improve cognitive function of offspring. However, the mechanisms through which maternal exercise might promote such effects are not well understood. The present study examined levels of brain-derived neurotrophic factor (BDNF) and absolute cell numbers in the hippocampal formation and cerebral cortex of rat pups born from mothers exercised during pregnancy. Additionally, we evaluated the cognitive abilities of adult offspring in different behavioral paradigms (exploratory activity and habituation in open field tests, spatial memory in a water maze test, and aversive memory in a step-down inhibitory avoidance task). Results showed that maternal exercise during pregnancy increased BDNF levels and absolute numbers of neuronal and non-neuronal cells in the hippocampal formation of offspring. No differences in BDNF levels or cell numbers were detected in the cerebral cortex. It was also observed that offspring from exercised mothers exhibited better cognitive performance in nonassociative (habituation) and associative (spatial learning) mnemonic tasks than did offspring from sedentary mothers. Our findings indicate that maternal exercise during pregnancy enhances offspring cognitive function (habituation behavior and spatial learning) and increases BDNF levels and cell numbers in the hippocampal formation of offspring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0147200PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714851PMC
July 2016

Relationship between seizure frequency and number of neuronal and non-neuronal cells in the hippocampus throughout the life of rats with epilepsy.

Brain Res 2016 Mar 4;1634:179-186. Epub 2016 Jan 4.

Departamento de Fisiologia, Universidade Federal de São Paulo (UNIFESP), Rua Botucatu 862, Ed. Ciências Biomédicas, 5°andar. Vila Clementino, CEP: 04023-900 São Paulo, SP, Brazil. Electronic address:

The relationship between seizure frequency and cell death has been a subject of controversy. To tackle this issue, we determined the frequency of seizures and the total number of hippocampal cells throughout the life of rats with epilepsy using the pilocarpine model. Seizure frequency varied in animals with epilepsy according to which period of life they were in, with a progressive increase in the number of seizures until 180 days (sixth months) of epileptic life followed by a decrease (330 days-eleventh month) and subsequently stabilization of seizures. Cell counts by means of isotropic fractionation showed a reduction in the number of hippocampal neuronal cells following 30, 90, 180 and 360 days of spontaneous recurrent seizures (SRS) in rats compared to their controls (about 25%-30% of neuronal cell reduction). In addition, animals with 360 days of SRS showed a reduction in the number of neuronal cells when compared with animals with 90 and 180 days of seizures. The total number of hippocampal non-neuronal cells was reduced in rats with epilepsy after 30 days of SRS, but no significant alteration was observed on the 90th, 180th and 360th days. The total number of neuronal cells was negatively correlated with seizure frequency, indicating an association between occurrence of epileptic seizures throughout life and neuronal loss. In sum, our results add novel data to the literature concerning the time-course of SRS and hippocampal cell number throughout epileptic life.
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http://dx.doi.org/10.1016/j.brainres.2015.12.055DOI Listing
March 2016
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