An enriched environment restored hippocampal cell patterns and enhanced short-term memory in gestational and breastfeeding protein-restricted male offspring

Abstract

Maternal undernutrition impacts neuron proliferation and differentiation, non-neuron onset, and cell migration, leading to changes in long-term offspring’s brain morphology and functionality. This study evaluated the effect of maternal protein intake restriction and enriched environment on the structural hippocampus and behavioral tests in 42-day-old male (low-protein) LP compared to NP (control) offspring. The study supports the selfish brain theory, which suggests that the brain maintains its mass despite significant changes in body weight. The hippocampus cellularity pattern was profoundly altered by reduced neuron numbers in the LP compared to the age-matched NP progeny, as revealed by the isotropic fractionation technique. Detailed data analysis revealed a discrepancy between behavioral tests and reduced hippocampal stem cells and neuron number, accompanied by increased non-neuronal cells, linked to a significant decrease in fear-reflecting behavior. However, the enriched environment (EE) was found to restore the altered neuronal hippocampi cellularity significantly and modify the discrimination ratio, enhancing the ability of both progenies to discriminate between novel and familiar objects in a short time, potentially associated with reversing abnormal hippocampus cell patterns. Immunohistochemistry further validated these findings, showing reduced progenitor cells, neurons, and total cells in mitosis in the LP offspring. At the same time, the enriched environment significantly increased hippocampal cell proliferation, a promising result that could lead to the recovery of neuronal stem cell numbers. The present data underscore the detrimental impact of gestational protein restriction on brain development and highlight EE’s potential to restore altered neuronal hippocampi cellularity, offering a hopeful outlook for future research and interventions.