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Non-invasive radiofrequency acts through an electromagnetic field that generates a thermal effect on adipose tissue without contact with the skin. The temperature in the subcutaneous reaches between 44°C to 45°C, which after 45 minutes of intervention causes apoptosis of adipocytes. The objective of this study is investigate the impact of non-invasive radiofrequency (RF) on global histone H3 acetylation and heat shock proteins (HSPs) 47 and 60 levels in the peripheral blood of healthy women. The participants were divided in control/sedentary (n = 10) and exercised/physically active (n = 10) groups and were submitted to 4 sessions of RF intervention (once a week; 45 min each session, total 4 sessions). In order to analyze the acute and long term effects, blood samples for biomarkers analysis were taken in 3 moments: before (T1), after the first session (T2) and after the last session (T3), while anthropometric measurements were taken before and after the treatment protocol. The intervention was not able to modulate the HSPs in both groups at any time, while a significant increase on global histone H3 levels was observed at T2 compared to T1 (p=0.047) in exercised group. Regarding anthropometric measurements, we observed a significant reduction in body mass and adipose mass in the exercised group in T3 when compared to T1. Non-invasive RF is able to improve anthropometric measurements in physically active healthy women. This response might be related to acute histone H3 hyperacetylation status and is not associated with the modulation of HSPs 47 and 60.

Fibromyalgia is a syndrome mainly diagnosed through patient medical history. These individuals may present symptoms, such as sleeping disorders, migraines, and widespread pain through the musculoskeletal system, resulting in less quality of life. Treatment for fibromyalgia is based on pharmacological and non-pharmacological options. Mind-body practices, such as Baduanjin Qigong, have been described as promising alternatives to better multiple symptoms presented by individuals with the condition. Searching for non-pharmacological alternatives that significantly increase the quality of life of these individuals, this study evaluates the alterations in epigenetic markers in short- and long-term after the practice of Baduanjin Qigong. The participants took part in presential sessions of Baduanjin Qigong twice a week for 8 weeks, as well as being encouraged to practice at home for 4 weeks. The evaluation of the biomarkers was made through the collection of blood samples before the first session, after the sessions in person and after the 4 weeks of practice at home. Fatigue, sleep quality and chronic pain were evaluated before the first sessions and at the end of the process, through the application of self-reported instruments: Fibromyalgia Impact Questionnaire (FIQ), Functional Assessment of Chronic Illness-Fatigue (FACIT), Pittsburgh Sleep Quality Index (PSQI) and Multidimensional Pain Evaluation Scale (EMADOR). As a result, significant improvements were found in quality of life, and in the symptoms of fatigue, sleep disturbance and in chronic pain in some regions of the body. In spite of the clinical-functional improvements, no significant alterations were found in the activity of histone acetyltransferase (HAT) enzymes after the intervention. The practice of Qigong approved to be a good alternative to improve the main symptoms of fibromyalgia in women, without involving modulation of HAT activity.

Background COPD physiopathology involves multiple pathways and evidence indicates that brain-derived neurotrophic factor (BDNF) is an important biomarker associated with parameters of COPD severity. This study aimed to analyze the time course of the effects of a pulmonary rehabilitation program (PRP) on BDNF levels and on functional status in COPD patients. Methods Patients were enrolled in a 24-session PRP. Exercise capacity, dyspnea, health-related quality of life, and the BODE index were assessed at baseline and after the PRP. BDNF plasma levels were measured at baseline (immediately before the 1st session), after the 1st session, and before and after the 24th session. Results Sixteen patients were included. A reduction in BDNF levels was observed after the 1st session and an increase was observed between the end of the 1st session and the beginning of the 24th session. The PRP promoted an improvement in exercise capacity and health-related quality of life and a reduction in dyspnea and the BODE index. Conclusion Exercise acutely reduced BDNF levels, an effect that was nullified by the overall intervention.

Depressive conditions precipitated by repeated stress are a major socio-economical burden in Western countries. Previous studies showed that ATP-P2X7 receptors (P2X7R) and adenosine A2A receptors (A2AR) antagonists attenuate behavioral modifications upon exposure to repeated stress. Since it is unknown if these two purinergic modulation systems work independently, we now investigated a putative interplay between P2X7R and A2AR. Adult rats exposed to restraint stress for 14 days displayed an anxious (thigmotaxis, elevated plus maze), depressive (anhedonia, increased immobility), and amnesic (modified Y maze, object displacement) profile, together with increased expression of Iba-1 (a marker of microglia “activation”) and interleukin-1β (IL1β) and tumor necrosis factor α (TNFα; proinflammatory cytokines) and an up-regulation of P2X7R (mRNA) and A2AR (receptor binding) in the hippocampus and prefrontal cortex. All these features were attenuated by the P2X7R-preferring antagonist brilliant blue G (BBG, 45 mg/kg, i.p.) or by caffeine (0.3 g/L, p.o.), which affords neuroprotection through A2AR blockade. Notably, BBG attenuated A2AR upregulation and caffeine attenuated P2X7R upregulation. In microglial N9 cells, the P2X7R agonist BzATP (100 μM) or the A2AR agonist CGS26180 (100 nM) increased calcium levels, which was abrogated by the P2X7R antagonist JNJ47965567 (1 μM) and by the A2AR antagonist SCH58261 (50 nM), respectively; notably JNJ47965567 prevented the effect of CGS21680 and the effect of BzATP was attenuated by SCH58261 and increased by CGS21680. These results provide the first demonstration of a functional interaction between P2X7R and A2AR controlling microglia reactivity likely involved in behavioral adaptive responses to stress and are illustrative of a cooperation between the two arms of the purinergic system in the control of brain function.

Parkinson's disease (PD) is a neurodegenerative disorder with significant motor disabilities and cognitive decline. Importantly, the imbalance of oxidative stress is related to PD physiopathology and progression. This study aimed to evaluate the impact of grape juice consumption associated with an aquatic exercise protocol on oxidative stress parameters and cognitive function in individuals with PD. The participants were randomized into two groups: grape juice group (GJG) and control group (CG) and were submitted to 4 weeks of an aquatic intervention (twice a week, approximately 60 minutes/session). The GJG also consumed 400 ml of grape juice per day (integral and conventional) during this period. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCa) questionnaire. For the analysis of oxidative stress markers, specifically lipid oxidative damage (TBARS), proteins (Carbonil), acid uric and the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase), blood collection were done before and after intervention. No changes were observed in cognitive function after intervention in both groups. Regarding biomarkers, a reduction of antioxidant enzymes, thiobarbituric acid reactive substances (TBARS) and uric acid was observed in both groups. However, only the GJG showed a significant reduction on protein oxidation levels after intervention. In conclusion, the consumption of grape juice associated with an aquatic exercise protocol might be consider an effective alternative to reduce the oxidative damage in PD, reinforcing the importance of this intervention in promoting beneficial impact in this population., Grape juice; Aquatic exercise; Oxidative stress; Cognition

A growing body of evidence has suggested that the imbalance of epigenetic markers and oxidative stress appears to be involved in the pathophysiology and progression of stroke. Thus, strategies that modulate these biomarkers might be considered targets for neuroprotection and novel therapeutic opportunities for these patients. Physical exercise has been reported to induce changes in these epigenetic markers and improve clinical outcomes in different populations. However, little is reported on this in post-stroke patients. The purpose of this study was to investigate the effect of a single exercise session with WalkAide functional electrical stimulation (FES) on cognitive performance, clinical functional parameters, oxidative stress and epigenetic modulation in post-stroke individuals. In this crossover design study, 12 post-stroke individuals aged 54-72 years of either sexes were included and subjected to a single session of exercise (45 minutes) without WalkAide functional electrical stimulation (EXE alone group), followed by another single session of exercise (45 minutes) with WalkAide functional electrical stimulation (EXE + FES group). The clinical functional outcome measures, cognitive performance and blood collections for biomarker measurements were assessed pre- and post-intervention. After intervention, higher Berg Balance Scale scores were obtained in the EXE + FES group than in the EXE alone group. There was no significant difference in the Timed Up and Go test results post-intervention between EXE alone and EXE + FES groups. After intervention, a better cognitive performance was found in both groups compared with before the intervention. After intervention, the Timed Up and Go test scores were higher in the EXE + FES group than in the EXE alone group. In addition, the intervention induced lower levels of lipid peroxidation. After intervention, carbonyl level was lower, superoxide dismutase activity and superoxide dismutase/catalase activity ratio were higher in the EXE + FES group, compared with the EXE group alone. In each group, both histone deacetylase (HDAC2) and histone acetyltransferase activities were increased after intervention compared with before the intervention. These findings suggest that a single exercise session with WalkAide FES is more effective on balance ability and cognitive performance compared with conventional exercise alone in post-stroke patients. This is likely to be related to the regulation of oxidative stress markers. The present study was approved by the Research Ethics Committee of the Methodist University Center-IPA (approval No. 2.423.376) on December 7, 2017 and registered in the Brazilian Registry of Clinical Trials-ReBEC (RBR-9phj2q) on February 11, 2019.

Studies indicate that gestational exercise practice positively impacts the offspring's cognition. Nevertheless, the influence of maternal resistance exercise, different periods of exercise practice, and the inter- and transgenerational effects involved in these responses are not known. This study sought to report the influence of the maternal practice of resistance exercise on offspring's cognitive function, exploring behavior, and neuroplastic and epigenetic marks in the hippocampus. Female Wistar rats were divided into four groups: sedentary (SS), exercised during pregnancy (SE), exercised before pregnancy (ES), and exercised before and during pregnancy (EE). Exercised rats were submitted to a resistance exercise protocol (vertical ladder climbing). Between postnatal days (P)81 and P85, male offspring were submitted to the Morris water maze test. At P85, the following analyses were performed in offspring's hippocampus: expression of IGF-1 and BrdU+ cells, global DNA methylation, H3/H4 acetylation, and HDAC2 amount. Only the offspring of SE mothers presented subtly better performance on learning and memory tasks, associated with lower HDAC2 amount. Offspring from ES mothers presented an overexpression of hippocampal neuroplastic marks (BrdU+ and IGF-1), as well as a decrease of DNA methylation and an increase in H4 acetylation. Offspring from EE mothers (continuously exercised) did not present modifications in plasticity or epigenetic parameters. This is the first study to observe the influence of maternal resistance exercise on offspring's brains. The findings provide evidence that offspring's hippocampus plasticity is influenced by exercise performed in isolated periods (pre- or gestationally) more than that performed continually.

Objective This study aimed to investigate the impact of an aquatic physical training program associated with grape juice (Vitis labrusca) consumption on functional outcomes, Brain-Derived Neurotrophic Factor (BDNF) and global histone H4 acetylation levels in peripheral blood from individuals with Parkinson's disease. Methods Nineteen participants were randomized to Aquatic Exercise (AQ, n = 9) and Aquatic Exercise + Grape Juice (AQ+GJ, n = 10) groups and performed to 4 weeks of an aquatic intervention (twice a week, approximately 60 min/session). The AQ+GJ groups also consumed 400 mL of grape juice per day during this period. Functional capacity (six-min walk test, 6MWT), mobility (The Timed Up and Go, TUG) and the risk of falls (Berg Balance Scale, BBS) were evaluated before and after intervention. In addition, blood collections were carried out for biomarker analysis (e.g. BDNF and global histone H4). Results The aquatic exercise program induced functional improvement in individuals with Parkinson's disease, specifically ameliorating their mobility and functional capacity. In addition, enhanced levels of BDNF and histone H4 acetylation were found after the intervention. Grape juice consumption did not potentiate these effects, since any significant differences between the AQ and AQ+GJ groups were not found in all analysed variables. Conclusions The present study provides important insights about aquatic exercise-modulated BDNF levels in individuals with Parkinson's disease in combination with functional improvements, suggesting that histone acetylation status may interact to dictate the molecular mechanisms involved in this response. Parkinson disease, aquatic exercise, BDNF, epigenetic, grape juice.

Parkinson's disease is a neurodegenerative disease. Oxidative stress, i.e., the imbalance between the generation of reactive oxygen species and the antioxidant defense capacity of the body, plays an important role in the pathogenesis of this disease. Physical exercise can regulate oxidative stress. The purpose of this study was to analyze the short- and long-term effects of an aquatic exercise program on oxidative stress levels in patients with Parkinson's disease. The aquatic exercise program was carried out during 1 month with two sessions per week (1 hour/session). Blood samples were collected at four different time points: pre-intervention, immediately, 48 hours, and 30 days after the first session of aquatic exercise program. Our results revealed that water-based programs modulated antioxidant enzyme activity, increased superoxide dismutase activity, reduced catalase activity, and increased the ratio of superoxide dismutase activity to catalase activity in patients with Parkinson's disease. Compared with pre-intervention and 48 hours after the first session of aquatic exercise program, superoxide dismutase activity was higher and catalase activity was lower immediately and 30 days after the first session. Our results demonstrated that aquatic exercise program could modulate oxidative stress, mainly by the effect of antioxidant enzyme activity. These results could better help understand the target of oxidative stress in Parkinson's disease. This study was approved by the Ethics Committee of Centro Universitario Metodista IPA (approval No. 1.373.911) on August 9, 2019 and registered with REBEC (registration number: RBR-6NJ4MK).

Introduction Some foods are also demonstrated benefits, such as anti-inflammatory, antioxidant, and ergogenic activity, similar to that of sports supplements. Grape juice has been considered an important source of polyphenols and these compounds could promote positive effects to the sports players. In this sense, the objective was to evaluate the effects of purple grape juice consumption on indicators of oxidative stress, inflammation, muscle damage, global histone H4 acetylation levels, and muscle strength and muscle power in volleyball athletes. Methods This is a randomized double-blind clinical trial in which 12 male volleyball players (16 ± 0.6 years old) participated in three different moments with match simulation: control (without beverage) (WB), grape juice (GJ) and placebo (PLA) (400 mL/day of grape juice or placebo (maltodextrin) for 14 days in a cross-over model). Before and immediately after each match, blood collection for analysis of indicators of systemic redox status, systemic concentrations of Interferon-γ (IFN- γ) and Interleukin-4 (IL-4), muscle damage, by Creatine Kinase (CK-NAC) and levels of global histone H4 acetylation were performed, as well as handgrip strength (HG) and lower limb power tests. Results Consumption of grape juice significantly reduced lipid peroxidation (p = 0.04) and Deoxyribonucleic Acid (DNA) damage (p = 0.01) after the match. IFN-γ levels, IL-4, CK-NAC, and histone H4 acetylation post-match did not alter with the grape juice consumption. Lower limb power improved after acute exercise in WB and GJ conditions (p Conclusion In this pilot trial, the intake of grape juice for two weeks seems to reduce the protein oxidation and DNA damage by intermittent physical exercise, without epigenetics influence.

Epidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3 g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats-SHR). Hyperlocomotion, recognition, and spatial memory disturbances were observed in adolescent SHR rats from both sexes. However, females showed lack of habituation and worsened spatial memory. Although caffeine was effective against recognition memory impairment in both sexes, spatial memory was recovered only in female SHR rats. Besides, female SHR rats showed exacerbated hyperlocomotion after caffeine treatment. SHR rats from both sexes presented increases in the BDNF, truncated and phospho-TrkB receptors and also phospho-CREB levels in the hippocampus. Caffeine normalized BDNF in males and truncated TrkB receptor at both sexes. These findings provide insight into the potential of caffeine against fully cognitive impairment displayed by females in the ADHD model. Besides, our data revealed that caffeine intake since childhood attenuated behavioral alterations in the ADHD model associated with changes in BDNF and TrkB receptors in the hippocampus.

The present study aimed to investigate the short and long-term effects of a concurrent exercise protocol on global histone H4 acetylation levels and inflammatory markers (interleukin-4 (IL-4), interleukin-6 (IL-6), interferon gamma (IFN-γ) and cortisol) in phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMC) and in peripheral blood of patients with schizophrenia (SZ), as well the intervention impact on anthropometric characteristics. Seventeen individuals were submitted to the intervention three times a week and blood samples were collected pre, 30, 60 and 90days after the intervention started. A remarkable reduction on body mass index and body mass were observed following intervention. The protocol also induced a histone H4 hypoacetylation status in PBMC all times evaluated when compared to the pre intervention period. Although the IL-4 and cortisol levels were not altered in response to the intervention, a reduction in IL-6 production during the 60 and 90days compared to the pre intervention period was observed. Finally, diminished IFN-γ production was found in the 90days period compared to the pre intervention and 30days after periods. In addition, systemic IL-6 levels were lower at 60 and 90days compared to the pre intervention. The concurrent exercise protocol was able to improve anthropometric characteristics in patients with SZ, engaging the modulation of cytokine and histone H4 acetylation levels.

This study aimed to evaluate the effectiveness of isolated treatment with retinoic acid and its combination with the microneedling technique in facial melasma, seeking to associate these results with possible oxidative damage. This is a blinded randomized clinical trial with 42 women with facial melasma (skin phototype I–IV), randomized into Group A (microneedling and 5% retinoic acid) or Group B (5% retinoic acid alone). Four procedures were applied with 15 days intervals (4 blood collections). Clinical improvement was assessed using the Melasma Area Severity Index (MASI). Serum oxidative stress levels were evaluated by protein oxidation (carbonyl), lipid peroxidation (TBARS) and sulfhydryl groups, as well as enzyme activities of superoxide dismutase (SOD) and catalase (CAT). The statistical analyzes were performed by generalized estimation equation (GEE). There was a reduction in MASI scale and TBARS levels in both groups over time (p

Caffeine prophylactically prevents mood and memory impairments through adenosine A(2A) receptor (A(2A)R) antagonism. A(2A)R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 +/- 7 %) and GABAergic (vGAT; -23 +/- 8 %) markers in the hippocampus. HM displayed higher A(2A)R density (72 +/- 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A(2A)R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 +/- 8 % vs. 21 +/- 5 % in controls) that was restored to control levels (30 +/- 10 %) by the A(2A)R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A(2A)R controlling synaptic glutamatergic function. NARSAD DARPA [09-68-ESR-FP-010] Fundacao para a Ciencia e para a Tecnologia [PTDC/SAU-NEU/122254/2010, PEst-C/SAU/LA0001/2013-2014] QREN [CENTRO-07-ST24-FEDER-002006] program Egide-Pessoa CAPES FCT (Ciencia sem Fronteiras)

The study aimed to compare the basal plasma levels of inflammatory markers (MCP-1, IL-1ra and IL-1β) in Parkinson Disease group (PDG) with control healthy subjects (control group, CG), as well to investigate the acute and chronic effects of an aquatic physiotherapy program on these biomarkers in PDG. Firstly, a rest blood sampling was taken from antecubital vein of the PD and CG. After, the PD individuals were submitted to a supervisioned aquatic physiotherapy program during 1 month, twice a week (60 min/session). In order to evaluate the acute and chronic effects of the intervention on the biomarkers, blood samples were in 4 times: before the exercise program (pre), immediately after the first session, 48 h after the exercise session and 1 month after the intervention. It was observed higher levels of the pro-inflammatory cytokines IL-1β and MCP-1 and reduced levels IL-1ra in PDG compared to the CG. Regarding the intervention effects in PDG, a remarkable reduction on IL-1β and MCP-1 levels at 48 h when compared to the basal were found. Furthermore, after 1 month, it was observed diminished levels of MCP-1 in combination to an increase on IL-1ra. Our data support the idea that an inflammatory status is linked to PD and that MCP-1 and IL-1ra could be taken as promising biomarkers in this condition. We also demonstrated that an aquatic physiotherapy program may offer a potential intervention able to attenuate immune responses in PD individuals in a short and long-term perspective.

Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders. Yet, how ATP and P2R contribute to neurodegeneration remains poorly defined. For that purpose, we now examined the contribution of extracellular ATP and P2Rs to glutamate-induced neurodegeneration. We found both in vitro and in vivo that ATP/ADP through the activation of P2Y1R contributes to glutamate-induced neuronal death in the rat hippocampus. We found in cultured rat hippocampal neurons that the exposure to glutamate (100 µM) for 30 min triggers a sustained increase of extracellular ATP levels, which contributes to NMDA receptor (NMDAR)-mediated hippocampal neuronal death through the activation of P2Y1R. We also determined that P2Y1R is involved in excitotoxicity in vivo as the blockade of P2Y1R significantly attenuated rat hippocampal neuronal death upon the systemic administration of kainic acid or upon the intrahippocampal injection of quinolinic acid. This contribution of P2Y1R fades with increasing intensity of excitotoxic conditions, which indicates that P2Y1R is not contributing directly to neurodegeneration, rather behaving as a catalyst decreasing the threshold from which glutamate becomes neurotoxic. Moreover, we unraveled that such excitotoxicity process began with an early synaptotoxicity that was also prevented/attenuated by the antagonism of P2Y1R, both in vitro and in vivo. This should rely on the observed glutamate-induced calpain-mediated axonal cytoskeleton damage, most likely favored by a P2Y1R-driven increase of NMDAR-mediated Ca2+ entry selectively in axons. This may constitute a degenerative mechanism shared by different brain diseases, particularly relevant at initial pathogenic stages., The present work was financed by Portuguese national funds via Fundação para a Ciência e a Tecnologia (FCT), under the projects EXPL/NEU-NMC/0671/2012 and PTDC/NEU-NMC/3567/2014 granted to R.J.R.; by Alzheimer Association under the project NIRG-15-361884 granted to R.J.R.; and by Santa Casa da Misericórdia and Prémio Maratona da Saúde granted to R.A.C. This work was also financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01-0145-FEDER-000008:BrainHealth2020, and through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT, under the project POCI-01-0145-FEDER-007440. A.P.S. was recipient of a postdoctoral fellowship (SFRH/BPD/91683/2012); J.M.M. was supported by a postdoctoral fellowship (SFRH/BPD/107903/2015). J.L. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV—2013-0317).

Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of caffeine have been described in adult animals with controversial findings about its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6months old) started to receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18-20months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A1 and A2A receptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A2A receptors increased with aging, both GFAP and adenosine A1 receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A2A receptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging.