Folic Acid Prevents Behavioral Impairment and Na+,K+-ATPase Inhibition Caused by Neonatal Hypoxia–Ischemia
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Folic acid plays an important role in neuroplasticity and acts as a neuroprotective agent, as observed in experimental brain ischemia studies. The aim of this study was to investigate the effects of folic acid on locomotor activity, aversive memory and Na+,K+-ATPase activity in the frontal cortex and striatum in animals subjected to neonatal hypoxia–ischemia (HI). Wistar rats of both sexes at postnatal day 7 underwent HI procedure and were treated with intraperitoneal injections of folic acid (0.011 μmol/g body weight) once a day, until the 30th postnatal day. Starting on the day after, behavioral assessment was run in the open field and in the inhibitory avoidance task. Animals were sacrificed by decapitation 24 h after testing and striatum and frontal cortex were dissected out for Na+,K+-ATPase activity analysis. Results show anxiogenic effect in the open field and an impairment of aversive memory in the inhibitory avoidance test in HI rats; folic acid treatment prevented both behavioral effects. A decreased Na+,K+-ATPase activity in striatum, both ipsilateral and contralateral to ischemia, was identified after HI; a total recovery was observed in animals treated with folic acid. A partial recovery of Na+,K+-ATPase activity was yet seen in frontal cortex of HI animals receiving folic acid supplementation. Presented results support that folic acid treatment prevents memory deficit and anxiety-like behavior, as well as prevents Na+,K+-ATPase inhibition in the striatum and frontal cortex caused by neonatal hypoxia–ischemia.
KeywordsHypoxia–ischemia Folic acid Inhibitory avoidance Na+,K+-ATPase Open-field test
This work was supported in part by grants from Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq—Brazil) and (Fundação de Amparo à Pesquisa do estado do Rio Grande do Sul (FAPERGS).
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