RESUMO
Objectives: Pyridoxine plays a key role in the development of the human nervous system. Several reports suggest that administration of high doses of pyridoxine can be helpful in improving disturbances such as anxiety and pyridoxine-dependent epilepsy, although it has also been associated with a proconvulsive action. In this study, we investigated in developing rats the effects of repeated administration of various doses of pyridoxine on anxiety-like behavior and the brain excitability-related phenomenon known as cortical spreading depression (CSD).Methods: From postnatal day (P) 7 to P27, Wistar rat pups received per gavage pyridoxine hydrochloride (1 mg/kg/day, or 5 mg/kg/day, or 10 mg/kg/day). On P60-70, the animals were tested in the elevated plus maze (EPM) to evaluate anxiety-like behavior. On P71-80, we recorded the CSD (4-hour recording session).Results: Compared with naïve (gavage-free) and saline-treated controls, pyridoxine-treated groups displayed a significant (p < 0.001) increase in CSD propagation velocity and amplitude of the CSD negative direct-current (DC)-shift, and a decrease in the CSD DC-shift duration. These effects were long-lasting and dose-dependent. In the EPM, no significant pyridoxine-associated effect was observed.Discussion: Our data demonstrate a novel action of pyridoxine on an electrical activity-related phenomenon (CSD) in the developing brain, confirming the hypothesis that the chronic treatment with pyridoxine early in life modulates CSD. Data on CSD propagation suggest that pyridoxine at a high dose might act as a prooxidant agent in the developing brain, a hypothesis that deserves further testing.
Assuntos
Ansiedade/fisiopatologia , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Piridoxina/administração & dosagem , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Masculino , Ratos WistarRESUMO
Guanosine (GUO) is a guanine-based purine that has been extensively described in the literature as an endogenous nucleoside with participation in brain cell signalling pathways. Here, we evaluated whether chronic treatment with exogenous guanosine during brain development altered behavioral and electrophysiological parameters in adulthood. Rat pups received a daily intraperitoneal injection of 10, 50 or 100â¯mg/ kg/day GUO, or saline solution or no treatment (naive group) from postnatal (P) day 7 to P27. At P 60-65 the animals were behaviorally tested in the Elevated Plus-Maze (EPM). On P90-100, the electrophysiological phenomenon known as cortical spreading depression (CSD) was recorded on the right cortical surface for 4â¯h. With the EPM task, GUO treatment was associated with a significant increase in rearing behavior and a non-significant trend towards anxiogenic behavior. In a dose-dependent manner, GUO significantly (pâ¯<â¯0.01) increased weight gain on P90, and reduced the CSD propagation velocity from 3.42⯱â¯0.10 and 3.43⯱â¯0.10â¯mm/min in the Naive and Vehicle controls, respectively, to 3.05⯱â¯0.12â¯mm/min, 2.87⯱â¯0.07â¯mm/min and 2.25⯱â¯0.25â¯mm/min in the groups treated with 10, 50 and 100â¯mg/kg/d GUO, respectively. The results confirmed the hypothesis that the chronic treatment with GUO early in life modulates CSD and body weight. Data on CSD propagation suggest that, besides its suppressing action on glutamatergic transmission (via enhancement of astrocytic glutamate uptake), GUO might act as an antioxidant in the brain, a hypothesis that deserves further exploration.