Administração de cumarina (4-metildinafetina) e seus efeitos na atividade física voluntária, comportamento e neurogênese de camundongos

Abstract

Coumarins are compounds that belong to the class of flavonoids, and can be synthesized or naturally occurring. 4-methyldinafetin is a synthesized coumarin, precursor of 4-methyl coumarin derivatives and has its physiological activities related to the antioxidant, neuroprotective and anti-inflammatory action. The present study aimed to verify the results of oral administration of coumarin 4-methyldaphenetine in processes related to voluntary physical activity, behavior and neurogenesis of C57BL6 mice. Thirty-two male, isogenic mice, approximately 8 weeks old, were used. The experiment lasted 30 days and the groups were separated into four groups: SV (Sedentary Vehicle), AFV (Physical Activity Vehicle), SCum (Sedentary Coumarin) and AFCum (Physical Activity Coumarin). Animals of the AFCum and SCum groups received a daily dose (30 mg/kg/wt) of 4-methyldinafetin via gavage. Groups AFV and SV only offer a vehicle solution. The AFCum and AFV groups were exposed to a volunteer activity wheel with computer registration throughout the experiment. All animals were screened intraperitoneally for 10 days on a bromodeoxyuridine-BrdU cell proliferation marker (50mg/kg-2x/day). Two tests were used to evaluate behavior patterns: Elevated Plus Maze Test (EPMT) and locomotor analysis and Object Recognition Test (ORT) for recognition memory patterns. On the 30th day of the experiment, all animals were anesthetized and euthanized for tissue collection. After the perfusion process, the brain was collected for neurogenesis analysis by immunofluorescence. Data were analyzed by means of ANOVA or Student's t-test for independent samples. The administration of 4-methyldinafetin decreased the volume of voluntary physical activity in the daytime period and minimized the effect of improvement in anxiety-related behavior generated by voluntary physical activity. No differences were observed in neurogenesis, recognition memory and the mean velocity / volume of voluntary physical activity related to the administration of 4-methyldinafetin. It was concluded that physical activity improves the behavior related to anxiety and the locomotor activity of mice exposed to the wheel of voluntary physical activity. Coumarin, however, influences the behavior and volume of physical activity related to the diurnal period, minimizing the behavioral effects of voluntary physical activity.