Iodine plusn-3 fatty acid supplementation augments rescue of postnatal neuronal abnormalities in iodine-deficient rat cerebellum

Abstract

High prevalence of hypothyroxinaemia in iodine-deficient (ID) mothers has serious implications for mental health of the progeny. Independent supplementation of iodine andn-3 fatty acids (FA) markedly improves growth and cognitive performance of school children. Discerning effects ofn-3 FA and iodine on the developing cerebellum have not been ascertained. The present study investigates effects of these two micronutrients separately as well as together in an ID rat model. We studied the effects of these micronutrients on progeny of ID dams by instituting the following supplementation diets: (1) low-iodine diet (LID), (2) LID+potassium iodide (KI), (3) LID+n-3 FA and (4) LID+KI+n-3 FA. Pups were investigated for morphological and biochemical parameters at the peak of cerebellar histogenesis on postnatal day (P) 16 and for neurobehavioural as well as motor coordination parameters at P40. Results indicate thatn-3 FA alone, without improvement in circulating thyroid hormone (TH), significantly improves functional, morphological and biochemical indices of the developing cerebellum. Further, results show that co-supplementation with iodine andn-3 FA rescues not only the loss of neurotrophic support, but also salvages motor coordination, memory and learning. This additive effect results in significantly improving neurotrophic support and seems to be mediated by parallel significant increase in TH receptor (TR)α and normalisation of TRβ, retinoic orphan receptor α and p75 neurotrophin receptor, as well as noteworthy prevention of apoptotic cell death and strengthening of anti-oxidative defence. The overall results indicate important mitigating role thatn-3 FA may play in enhancing TH nuclear receptor-mediated signalling in the developing cerebellum.