Presented at the Neonatal Society 2002 Summer Meeting.

Kodas E, Vancassel S*, Guilloteau D, Chalon S

INSERM U316, Laboratoire de Biophysique Médicale et Pharmaceutique, Université François Rabelais, 31, Avenue Monge, 37200 Tours, France and * LNSA, INRA Jouy-en-Josas

Synaptogenesis and neurogenesis require high incorporation of n-3 PUFAs in cerebral membranes during the perinatal period. The precise need of these essential PUFAs for optimal brain function can be clarified through animal models. In rodents, chronic n-3 PUFA deficiency affects the fatty acid (FA) composition of cerebral membranes and impairs performances in learning and behavioural tasks. As these tasks are under the dependence of monoaminergic neurotransmission systems, we suggested that this deficiency could disturbed their regulation. Our recent investigations showed altered FA composition and abnormal functioning of the mesocortico-limbic dopaminergic pathway in this model.

The aim of this study was therefore to determine (i) whether these biochemical and neurochemical modifications could be reversed by normalising n-3 PUFA supply in deficient animals, (ii) if this reversibility could occur whatever the stage of life at which the regimen was shifted. Reversal diet has been supplied to deficient rats at birth, 7, 14 or 21 days of age (group D0, D7, D14, D21). At the adulthood, we determined in the prefrontal cortex and nucleus accumbens (i) the FA composition of neuronal phospholipids, (ii) the level of stimulated dopamine release using dual-probe microdialysis technique. The recovery of FA composition was complete for all dietary groups.

For D0, D7 and D14 groups, the level of stimulated dopamine release was identical to controls, whereas it was similar to deficient group for D21. The shift of n-3 PUFA deficient diet to a normal diet allowed biochemical brain recovery whatever the stage of repletion, whereas restoration of dopaminergic function was dependant of the developmental stage of repletion. This suggested that neurochemical function could not be directly related to biochemical composition of neuronal membranes. The degree of brain maturation seems play a critical role in the ability to recover neurochemical functions altered by n-3 PUFA deficiency.