Effects of undernourishment, recurrent seizures and enriched environment during early life in hippocampal morphology

•Undernourishment decreased neuronal density in CA1 and CA3 subfield of hippocampus.•Seizures decreased neuronal density in CA1 subfield of hippocampus.•Enriched environment increases hippocampal volume and thickness of CA1 pyramidal layer.

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.