Circulating extracellular vesicles in the aging process: impact of aerobic exercise.

Our aim was to investigate transitory and delayed exercise effects on serum extracellular vesicles (EVs) in aging process. Male Wistar rats of 3-, 21-, and 26-month old were allocated into exercised and sedentary groups. The exercise protocol consisted in a daily moderate treadmill exercise (20 min daily during 2 weeks). Trunk blood was collected 1 and 18 h after the last exercise session, and circulating EVs were obtained. CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome, a subtype of EVs. In addition, the quantification of amyloid-ß (Aß) levels and the oxidative status parameters, specifically reactive species content, superoxide dismutase (SOD) activity, and SOD1 content were evaluated. Aged rats showed reduced CD63 levels and increased AChE activity in circulating exosomes compared to young ones. Moreover, higher reactive species levels were found in circulating EVs of aged rats. Delayed exercise effects were observed on peripheral EVs, since CD63, reactive species content, and AChE activity were altered 18 h after the last exercise session. Our results suggest that the healthy aging process can modify circulating EVs profile, and exercise-induced beneficial effects may be related to its modulation on EVs.

The Aging Process Alters IL-1ß and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid.

OBJECTIVE(S): The aim of this study was to investigate exosomal markers and inflammatory cargo of extracellular vesicles (EVs) obtained from cerebrospinal fluid (CSF) and plasma in the aging process. We also studied the inflammatory cargo by quantifying IL-1ß levels. METHODS: Male Wistar rats, aged 3 and 21 months, were used (n = 12 in each group). The CSF and plasma of animals were collected, and isolation of EVs was performed using a commercial kit. Total protein concentration, acetylcholinesterase (AChE) activity, and CD63 and IL-1ß levels were evaluated. RESULTS: AChE activity in EVs increased in both samples, specifically in the circulating EVs and those in the CSF of the older group. An age-related increase was observed in CD63 levels in EVs from the CSF but a decrease was observed in plasma EVs of the older group. Student's t test showed that the young adult rats had significantly higher circulating IL-1ß levels in the EVs compared to the aged ones, without any effect on central content. CONCLUSION: Our data suggest that the normal aging process causes different changes in the profiles of central and circulating EVs. Altered IL-1ß levels in circulating EVs can be linked, at least partly, to age-related inflammatory conditions, and a disruption of the CFS exosomes in aged rats, evaluated by CD63 levels, can be related to susceptibility to neurodegenerative disorders.

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.

Treadmill exercise alters histone acetyltransferases and histone deacetylases activities in frontal cortices from wistar rats.

Studies have pointed out the relationship between neuroprotective exercise effects and epigenetic mechanisms on the hippocampus. Considering the role of frontal cortex on brain functions, we investigated the impact of different exercise protocols on enzymatic system involved with histone acetylation status, histone acetyltransferases (HATs), and histone desacetylases (HDACs) in frontal cortices from Wistar rats. Male Wistar rats aged 3 months were submitted to a single session or a daily running protocol during 2 weeks. The single session enhanced HAT activity, while the moderate daily exercise protocol reduced the HDAC activity. Our results indicate that frontal cortex is susceptible to epigenetic modulation following exercise and that both exercise protocols seem to induce a histone hyperacetylation condition in this brain area.

Treadmill exercise induces age-related changes in aversive memory, neuroinflammatory and epigenetic processes in the rat hippocampus.

It has been described that exercise can modulate both inflammatory response and epigenetic modifications, although the effect of exercise on these parameters during the normal brain aging process yet remains poorly understood. Here, we investigated the effect of aging and treadmill exercise on inflammatory and epigenetic parameters specifically pro and anti-inflammatory cytokines levels, activation of NF-kB and histone H4 acetylation levels in hippocampus from Wistar rats. Additionally, we evaluated aversive memory through inhibitory avoidance task. Rats of 3 and 20 months of age were assigned to non-exercised (sedentary) and exercised (running daily for 20 min for 2 weeks) groups. The effect of daily forced exercise in the treadmill was assessed. The levels of inflammatory and epigenetic parameters were determined 1h, 18 h, 3 days or 7 days after the last training session of exercise. It was observed an age-related decline on aversive memory, as well as aged rats showed increased hippocampal levels of inflammatory markers, such as TNFα, IL1-ß and NF-kB and decreased IL-4 levels, an anti-inflammatory cytokine. Moreover, lower levels of global histone H4 acetylation were also observed in hippocampi from aged rats. Interestingly, there was a significant correlation between the biochemical markers and the inhibitory avoidance test performance. The forced exercise protocol ameliorated aging-related memory decline, decreased pro-inflammatory markers and increased histone H4 acetylation levels in hippocampi 20-months-old rats, while increased acutely IL-4 levels in hippocampi from young adult rats. Together, these results suggest that an imbalance of inflammatory markers might be involved to the aging-related aversive memory impairment. Additionally, our exercise protocol may reverse aging-related memory decline through improving cytokine profile.

Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat.

Physical activity impacts functional recovery following stroke in humans, however its effects in experimental animals submitted to chronic cerebral hypoperfusion have not been investigated. The aim of this study was to evaluate the therapeutic potential of exercise, as assessed by cognitive activity in the Morris water maze and the brain oxidative status, through measurement of macromolecules damage, TBARS levels and total cellular thiols, as well as antioxidant enzymes in hippocampus, striatum and cerebral cortex. Adult male Wistar rats were submitted to the modified permanent bilateral occlusion of the common carotid arteries (2VO) method, with right common carotid artery being first occluded, and tested 3 months after the ischemic event. The effects of three different exercise protocols were examined: pre-ischemia, post-ischemia and pre+post-ischemia. Physical exercise consisted of sessions of 20-min, 3 times per week during 12 weeks (moderate intensity). Rats were submitted to cognitive assessment, in both reference and working spatial memory and after the last testing session were sacrificed to have oxidative stress parameters determined. Hypoperfusion caused a significant cognitive deficit in both spatial water maze tasks and this effect was reversed in rats receiving exercise protocol post and pre+post the ischemic event. Moreover, forced regular treadmill exercise regulated oxidative damage and antioxidant enzyme activity in the hippocampus. These results suggest that physical exercise protects against cognitive and biochemical impairments caused by chronic cerebral hypoperfusion.

Time-dependent effects of treadmill exercise on aversive memory and cyclooxygenase pathway function.

Exercise induces brain function adaptations and improves learning and memory; however the time window of exercise effects has been poorly investigated. Studies demonstrate an important role for cyclooxygenase-2 (COX-2) pathway function in the mechanisms underlying memory formation. The aim of present work was to investigate the effects of treadmill exercise on aversive memory and COX-2, PGE(2) and E-prostanoid receptors contents in the rat hippocampus at different time points after exercise has ended. Adult male Wistar rats were assigned to non-exercised (sedentary) and exercised (running daily for 20min, for 2weeks) groups. The inhibitory avoidance task was used to assess aversive memory and the COX-2, PGE(2) and E-prostanoid receptors (EP1, EP2, EP3 and EP4) levels were determined 1h, 18h, 3days or 7days after the last training session of treadmill exercise. The step down latency in the inhibitory avoidance, COX-2 and EP4 receptors levels were acutely increased by exercise, with a significant positive correlation between aversive memory performance and COX-2 levels. Increased EP2 content decreased PGE(2) levels were observed 7days after the last running session. The treadmill exercise protocol facilitates inhibitory avoidance memory and induces time-dependent changes on COX-2 pathways function (COX-2, PGE(2) and EP receptors).

Effect of landfill leachate on oxidative stress of brain structures and liver from rodents: modulation by photoelectrooxidation process.

The decomposition of solid waste in landfill is responsible for the formation of leachate, a dark liquid with an unpleasant odor; studies investigating its toxicity on mammals are rare. Oxidative stress has been considered as an important biochemical mechanism of the toxicity of several xenobiotics. The aim of this study was to evaluate the effects of landfill leachate on oxidative parameters in striatum, hippocampus and liver homogenates of mice and rats. In order to propose a clean technology for the treatment of leachate, we also investigated the effects of landfill leachate submitted to photoelectrooxidation process (PEO). The homogenates of cerebral structures and liver of Swiss albino mice and Wistar rats were incubated with different concentrations of non-PEO landfill leachate and PEO-treated landfill leachate. After the incubation, the levels of free radicals, determined by 2',7'-dichlorofluorescein diacetate probe, and the lipoperoxidation, quantified by the thiobarbituric acid reactive substances, were evaluated. There was an increase on the levels of free radicals in striatum of both mice and rats when exposed to non-PEO leachate. Moreover, PEO-treated leachate increased the lipoperoxidation in striatum homogenates from rodents. However, both leachates did not alter any of the parameters evaluated in the hippocampus. In the liver, the incubation with leachates induced an augment on levels of free radicals only in samples of mice. In addition, PEO-treated leachate increased the lipoperoxidation indexes in the liver of mice and rats. These results suggest that the landfill leachate can induce an oxidative stress state in the liver and the striatum of rodents. Additionally, the PEO process was unable to efficiently alter the toxic compounds of landfill leachate.

Correlation Between Inflammatory and Epigenetic Marks With Aerobic Performance in 10-km Runners.

Purpose: Our goals were to evaluate the effect of a 10-km running trial on inflammatory and epigenetic markers of 10-km runners and correlate the biochemical findings with anthropometric variables and performance. Methods: Twenty trained 10-km runners and seven sedentary male volunteers were recruited. Venous blood samples were collected at different times: under resting conditions, before the 10 Km race, and immediately after the finish. Inflammatory markers (IL-6, IL-10, and IL-ß) and cortisol levels were evaluated in plasma, while DNA methyltransferases (DNMT1 and DNMT3b) contents were measured in peripheral blood mononuclear cells (PBMCs). Results: Higher levels of plasma IL-6 levels were observed in 10-km runners compared to the sedentary group. After the trial, the runners had a significant increase on IL-6, IL-10, and cortisol plasma levels compared to baseline. Conclusion: Our findings suggest that inflammatory profile, but not DNMT content, influences aerobic performance in 10-km runners.

Acrobatic exercise recovers object recognition memory impairment in hypoxic-ischemic rats.

Neonatal hypoxia-ischemia (HI) can lead to cognitive impairments and motor dysfunction. Acrobatic exercises (AE) were proposing as therapeutic option to manage HI motor deficits, however, the cognitive effects after this treatment are still poorly understood. Therefore, we evaluated the effects of AE protocol on memory impairments and brain plasticity markers after Rice-Vannucci HI rodent model. Wistar rats on the 7th postnatal day (PND) were submitted to HI model and after weaning (PND22) were trained for 5 weeks with AE protocol, then subsequently submitted to cognitive tests. Our results showed recovery in novel object recognition (NOR) memory, but not, spatial Morris Water Maze (WM) memory after AE treatment in HI rats. BDNF and synaptophysin neuroplasticity markers indicate plastic alterations in the hippocampus and striatum, with maintenance of synaptophysin despite the reduction of total volume tissue, besides, hippocampal HI-induced ipsilateral BDNF increased, and striatum contralateral BDNF decreased were noted. Nevertheless, the exercise promoted functional recovery and seems to be a promising strategy for HI treatment, however, future studies identifying neuroplastic pathway for this improvement are needed.

Methylphenidate treatment increases hippocampal BDNF levels but does not improve memory deficits in hypoxic-ischemic rats.

BACKGROUND: Methylphenidate (MPH) is a stimulant drug mainly prescribed to treat cognitive impairments in attention-deficit/hyperactivity disorder (ADHD). We demonstrated that neonatal hypoxia-ischemia (HI) induced attentional deficits in rats and MPH administration reversed these deficits. However, MPH effects on memory deficits after the HI procedure have not been evaluated yet. AIMS: We aimed to analyze learning and memory performance of young hypoxic-ischemic rats after MPH administration and associate their performance with brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex and hippocampus. METHODS: Male Wistar rats were divided into four groups (n=11-13/group): control saline (CTS), control MPH (CTMPH), HI saline (HIS) and HIMPH. The HI procedure was conducted at post-natal day (PND) 7 and memory tasks between PND 30 and 45. MPH administration (2.5 mg/kg, i.p.) occurred 30 min prior to each behavioral session and daily, for 15 days, for the BDNF assay (n=5-7/group). RESULTS: As expected, hypoxic-ischemic animals demonstrated learning and memory deficits in the novel-object recognition (NOR) and Morris water maze (MWM) tasks. However, MPH treatment did not improve learning and memory deficits of these animals in the MWM-and even disrupted the animals' performance in the NOR task. Increased BDNF levels were found in the hippocampus of HIMPH animals, which seem to have been insufficient to improve memory deficits observed in this group. CONCLUSIONS: The MPH treatment was not able to improve memory deficits resulting from the HI procedure considering a dose of 2.5 mg/kg. Further studies investigating different MPH doses would be necessary to determine a dose-response relationship in this model.

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.

Aging process alters hippocampal and cortical secretase activities of Wistar rats.

A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by ß- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging.

Effect of tannery effluent on oxidative status of brain structures and liver of rodents.

Oxidative stress has been considered as a central mechanism of toxicity induced by xenobiotics. Previously, it was demonstrated that mice exposed to tannery effluent showed an anxiety-like behavior, without any comparable behavioral effects in rats. The aim of the present study was to investigate the impact of tannery wastewater on oxidative status in in vitro and in vivo assays with two mammal species, mice and rats. Specifically, homogenates of two brain areas and the liver were incubated with tannery wastewater; reactive species and lipid peroxidation levels and antioxidant enzyme activities were detected. In addition, the effects of in vivo exposure of mice to tannery effluents on and lipid peroxidation levels and the total reactive antioxidant capacity in brain areas and liver. Brain areas, the hippocampus and frontal cortex, and the liver of mice exposed to tannery wastewater showed oxidative stress. Our data suggest that divergent species-dependent hepatic enzymes adaptations, such as glutathione peroxidase and glutathione S-transferase activities, induced by tannery effluent could explain previous behavioral findings.

BDNF levels are increased in peripheral blood of middle-aged amateur runners with no changes on histone H4 acetylation levels.

Our aim was to compare the basal levels of plasma brain-derived neurotrophic factor (BDNF) and global histone H4 acetylation in peripheral blood mononuclear cells (PBMCs) of healthy amateur runners (EXE group) with sedentary individuals (SED group) as well as to investigate the acute effect of a running race on these markers in the EXE group. Five days before the race, all participants were submitted to a basal blood collection. On the race day, two blood samples were collected in the EXE group before the running started and immediately at the end. In the basal period, a significant increase of plasma BDNF levels in the EXE individuals when compared to the SED group (p = 0.036) was demonstrated, while no difference in global histone H4 acetylation levels was observed. These parameters were unaltered in the EXE group after the race. The increased levels of BDNF might be linked to healthy middle-aged runners' phenotype.

Effects of tannery wastewater exposure on adult Drosophila melanogaster.

Our aim was to evaluate the effects of exposure to tannery wastewater on mortality and/or antioxidant enzyme system in adult wild-type Canton-S Drosophila melanogaster. Exposure to tannery wastewater induced a concentration-dependent lethality in adult Canton-S flies. Tannery wastewater was able to alter antioxidant enzyme activities, specifically glutathione peroxidase-like and glutathione S-transferase, in adult Canton-S D. melanogaster. We conclude that D. melanogaster is a reliable model to evaluate the toxicity induced by tannery wastewater.

Caminhando pelo hospital: estratégia para articulação do ensino teóricoprático na formação em Enfermagem / Walking through the hospital: strategy for the articulation of theoretical-practical teaching in Nursing education / Paseo por el hospital: estrategia para la articulación de la enseñanza teórico-práctica en la formación de Enfermería

Objetivo: Descrever a atividade de extensão universitária "Caminhando pelo hospital". Métodos: Trata-se de um relato de experiência da atividade de extensão universitária alocada em um Serviço de Radiologia de um hospital universitário do sul do Brasil no período de 2017 a 2020. Resultados: O relato apresenta as características do projeto do qual já participaram 55 alunos da graduação em enfermagem, abordando "Motivação para o desenvolvimento e implementação do projeto", "Estratégias para o desenvolvimento da atividade", "Articulação do ensino teórico-prático da graduação em enfermagem por meio das atividades desenvolvidas pelos extensionistas" e as potencialidades dessa iniciativa. Conclusão: O projeto contribuiu na formação dos acadêmicos, pelo contato com a realidade profissional como diferencial para o aprendizado, ao possibilitar a observação da atuação da equipe de enfermagem em um ambiente hospitalar. Esperase que essa experiência possa estimular outras instituições universitárias a implementarem essa iniciativa. (AU)

Objective: To describe the university extension activity "Walking through the hospital". Methods: This is an experience report of the university extension activity allocated in a Radiology Service of a university hospital in southern Brazil in the period from 2017 to 2020. Results: The report presents the characteristics of the project in which 55 undergraduate nursing students have already participated, addressing "Motivation for the development and implementation of the project", "Strategies for the development of the activity", "Articulation the theoretical-practical teaching of undergraduate nursing through the activities developed by extensionists" and the potential of this initiative. Conclusion: The project contributed to the formation of the students, through contact with professional reality as a differential for learning, by allowing the observation of the nursing team's performance in a hospital environment. It is hoped that this experience can stimulate other university institutions to implement this initiative. (AU)

Objetivo: Describir la actividad de extensión universitaria "Caminando por el hospital". Métodos: Este es un informe de experiencia de la actividad de extensión universitaria asignada en un Servicio de Radiología de un hospital universitario del sur de Brasil en el período de 2017 a 2020. Resultados: El informe presenta las características del proyecto en el que ya han participado 55 estudiantes de enfermería de pregrado, abordando "Motivación para el desarrollo e implementación del proyecto", "Estrategias para el desarrollo de la actividad", "Enlace de la enseñanza teórico-práctica de la enfermería de pregrado a través de actividades desarrolladas por extensionista" y las potencialidades de esta iniciativa. Conclusión: El proyecto contribuyó a la formación de académicos, a través del contacto con la realidad profesional como diferencial para el aprendizaje, al posibilitar la observación del desempeño del equipo de enfermería en un ambiente hospitalario. Se espera que esta experiencia anime a otras instituciones universitarias a implementar esta iniciativa. (AU)

An evaluation of aversive memory and hippocampal oxidative status in streptozotocin-induced diabetic rats treated with resveratrol.

The present study evaluated the effects of streptozotocin (STZ)-induced diabetes on aversive memory, free radical content and enzymatic antioxidant activity in the hippocampus of adult Wistar rats submitted to oral treatment with resveratrol. Animals were divided into eight groups: non-diabetic rats treated with saline (ND SAL), non-diabetic rats treated with resveratrol at a dose 5mg/kg (ND RSV 5), non-diabetic rats treated with resveratrol at a dose 10mg/kg (ND RSV 10), non-diabetic rats treated with resveratrol at a dose 20mg/kg (ND RSV 20), diabetic rats treated with saline (D SAL), diabetic rats treated with resveratrol at a dose 5mg/kg (D RSV 5), diabetic rats treated with resveratrol at a dose 10mg/kg (D RSV 10) and diabetic rats treated with resveratrol at a dose 20mg/kg (D RSV 20). The animals received oral gavage for 35days. The contextual fear conditioning task was performed to evaluate aversive-based learning and memory. The oxidative status was evaluated in the hippocampus, by measuring the free radical content - using a 2',7'-dichlorofluorescein diacetate probe - and enzymatic antioxidant activities, such as superoxide dismutase and glutathione peroxidase. Our main behavioral results demonstrated that rats from the D RSV 10 and D RSV 20 groups showed an increase in freezing behavior when compared, respectively, to the ND RSV 10 (p<0.01) and ND RSV 20 (p<0.05). Oxidative stress parameters remained unchanged in the hippocampus of all the experimental groups. In contrast to previous experimental findings, our study was unable to detect either cognitive impairments or oxidative stress in the hippocampus of the diabetic rats. We suggest additional long-term investigations be conducted into the temporal pattern of STZ-induced diabetic disruption in memory and hippocampal oxidative status, as well as the effects of resveratrol on these parameters, in a time and dose-dependent manner.