Perinatal Brain Docosahexaenoic Acid Concentration Has a Lasting Impact on Cognition in Mice

Background: Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22: 6n-3)], an omega-3 fatty acid [omega-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by omega-3 FA supplementation. Objective: The objective was to test whether there is a critical period for providing omega-3 FA to correct cognitive deficits caused by developmental omega-3 FA deprivation in mice. Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr] were fed an omega-3 FA-deficient diet containing 0.04% a-linolenic acid [ALA (18: 3n-3)], and their offspring were fed the same deficient diet (Def group) or changed to an omega-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively. Results: Maternal dietary omega-3 FA deprivation decreased DHA by > 50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk. Conclusion: Developmental deprivation of brain DHA by dietary omega-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.