ABSTRACT
It has been recently shown that enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and recurrent seizures. We investigated the hippocampal morphological effects of recurrent seizures and undernourishment early in life in Wistar rats and the possible benefits produced by the enriched environment in these conditions. The morphological parameters stereologically evaluated were hippocampal volume, thickness of pyramidal stratum of the CA1 subfield and neuronal and glial densities in the same subfield. Male Wistar rats were divided into eight groups including nourished, nourished+enriched environment, nourished+recurrent seizures, nourished+recurrent seizures+enriched environment, undernourished, undernourished+enriched environment, undernourished+recurrent seizures and undernourished+recurrent seizures+enriched environment. Undernourishment model consisted in nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures group were induced by flurothyl three times per day. Enriched environment groups were exposed between P21 and P51. Our main findings were: (1) animals submitted to the enriched environment showed an increased hippocampal volume; (2) enriched environment promotes increases in the thickness of the pyramidal layer in hippocampal CA1 subfield in animals nourished and undernourished with recurrent seizures; (3) undernourishment during early development decreased neuronal density in CA1 and CA3 subfields. Our findings show that these three conditions induces important changes in hippocampal morphology, the most deleterious changes are induced by undernourishment and recurrent seizures, while more beneficial morphological changes are produced by enriched environment.
Subject(s)
Environment , Hippocampus/pathology , Malnutrition/complications , Seizures/nursing , Seizures/pathology , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Cell Count , Convulsants/toxicity , Disease Models, Animal , Female , Flurothyl/toxicity , Male , Neuroglia/pathology , Neurons/pathology , Pregnancy , Rats , Rats, Wistar , Seizures/chemically inducedABSTRACT
We recently reported that early undernourishment and seizures to the rat brain resulted in morphological changes and progressive learning and memory disability, which started at around 6 week later and is representative of human adolescence. The purpose of the present study was to examine whether enriched environmental can recovery this slowly progressing deficits in early undernourished and in two different models for seizures. Undernourished groups were maintained on a nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures (RS) groups were exposed to three seizures per day, while status epilepticus (SE) groups experienced status epilepticus at P16, both induced by flurothyl. Next, animals were exposed to enriched environment between P30 and P60. Beginning at P61, all groups were trained and tested in the Morris water maze (MWM). Enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and SE.
Subject(s)
Environment , Malnutrition/complications , Maze Learning/physiology , Retention, Psychology/physiology , Seizures , Spatial Behavior/physiology , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Convulsants/toxicity , Disease Models, Animal , Female , Flurothyl/toxicity , Male , Maze Learning/drug effects , Pregnancy , Rats , Reaction Time , Retention, Psychology/drug effects , Seizures/complications , Seizures/etiology , Seizures/nursing , Spatial Behavior/drug effects , Time FactorsABSTRACT
We evaluate the influence of different malnutrition paradigms (intra-uterine x extra-uterine) in body and brain weight, in seizure threshold and in hippocampus morphometry, in developing rats. Intra-uterine malnutrition model consisted in reduction by half of the ration offered to pregnant female; extrauterine malnutrition consisted of progressive limitation of lactation, from P2 to P15. Seizure induction was accomplished by exposure to flurothyl, at P15. At the same day animals were sacrificed. Morphometric analysis was based on hippocampal pyramidal and granular cells estimate number, through volume calculation and cellular density. Extra-uterine malnutrition significantly reduced pups body and brain weight, seizure threshold and neuronal number in CA4 region only. Intra-uterine malnutrition reduced neuronal number in CA2, CA4 and DG regions regarding well-nourished and extra-uterine malnourished animals. In CA3, CA4 and dentate gyrus, a significant cell increase was observed in groups exposed to seizures, regarding similar control groups.