Astaxanthin and DHA supplementation modulates the perinatal undernutrition induced impairment of cognitive behaviour and synaptic plasticity in the adult life -Exploring the molecular mechanism

Abstract

Maternal nutrition has been recognized as a significant component of brain growth and maturation in most mammalian species. Hence, timely intervention with suitable nutraceuticals would provide long-term health benefits. Here, we aimed to unravel the molecular mechanism of perinatal undernutrition-induced impairments in cognition and synaptic plasticity, employing animal model based on dietary nutraceutical supplementation. We treated prenatal, postnatal, and perinatally undernourished dams with Astaxanthin (AsX) and Docosahexaenoic acid (DHA). We evaluated the cognitive function and synaptic plasticity by exposing the pups to behavioural tests during their adult life. In addition, we assessed the expression of genes in the hippocampus related to cognitive function and synaptic plasticity. Our results showed the downregulation of Brain-derived neurotrophic factor (BDNF), Neurotrophin-3 (NT-3), cAMP response-element-binding protein (CREB), and Uncoupling protein-2 (UCP2) gene expressions in perinatally undernourished animals in their adult life which was significantly modulated by AsX and DHA. Maternal AsX and DHA supplementation ameliorated the undernutrition-induced learning impairment in novel object recognition (NOR) tests and partially baited radial arm maze (RAM) 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. AsX and DHA supplementation upregulated BDNF, NT-3, and CREB gene expressions in perinatally undernourished rats, which are involved in intracellular signalling cascades like MAPK, PI3K, and PLC. The results of our study provide new insights into triggering neuronal differentiation, survival, and plasticity, indicating that the perinatal period is the critical time for reversing undernutrition-induced cognitive impairment.