Developmental docosahexaenoic and arachidonic acid supplementation improves adult learning and increases resistance against excitotoxicity in the brain

Through metabolic imprinting mechanisms a number of bioactive molecules including polyunsaturated fatty acids affect brain functions in the developmental age and longer-lasting beneficial effects are expected. In this study pregnant rats were offered diets either containing no docosahexaenoic acid (DHA) and arachidonic acid (AA) (Placebo diet) or an excess amount of these long chain polyunsaturated fatty acids (LC-PUFA) (Supplement diet) up to the time of weaning. Bilateral N-methyl-D-aspartate (NMDA) induced neurodegeneration in the entorhinal cortex of offspring in the age of 4 months was used as a tool to investigate the neuroprotective property of the developmentally supplemented DHA and AA treatments. Hippocampus-dependent spatial learning was measured in Morris water maze and the extent of neuronal lesion in the injected brain area was evaluated. Under baseline condition, in intact or sham-lesioned rats, the Morris water maze performance was superior in the supplemented group compared to the placebo controls. NMDA-lesion in the entorhinal cortex area decreased spatial learning in the supplement-treated rats while insignificantly diminished it in the placebo controls. The same supplementation attenuated the lesion size induced by the NMDA injection into the entorhinal and ventral hippocampal areas. We concluded that LC-PUFA supplementation during fetal and early postnatal development results in long-term enhancement of spatial learning ability of the offspring and offers resistance against excitotoxic brain lesion which lasts up to the adult age.