A Mechanistic Approach to Elucidate the Molecular Basis of Amelioration of Perinatal Undernutrition Induced Cognitive Impairment Using Astaxanthin and DHA in the Adult Life of Albino Wistar Rats

Maternal nutrition has been recognized as a significant component of brain growth and maturation in most mammalian species. Here, we showed that the downregulation of BDNF, NT-3, CREB, and UCP2 gene expressions in perinatally undernourished animals in their adult life was mitigated by Astaxanthin and DHA. We also found that maternal undernutrition reduced the pups’ weight at birth considerably and remained decreased throughout the study. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in NOR test and partially baited radial arm maze tasks. Furthermore, the expressions of Synapsin-1 and PSD-95 decreased in perinatally undernourished groups compared to control, and AsX-DHA treated groups at CA1, CA2, CA3, and DG, respectively. Our results identified a signalling pathway that mediates perinatal undernutrition stress-induced cognitive decline via intracellular signalling cascades like MAPK, PI3K, and PLC, triggering neuronal differentiation, survival, and plasticity, indicating the critical time for the reversal of undernutrition-induced cognitive impairment.