Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: critical role of developmental stage

Previous investigations have shown that the lipid composition of cerebral membranes and dopaminergic neurotransmission are changed under chronic alpha-linolenic acid diet deficiency in the rat. This study investigated whether these changes could be reversed and if the stage of brain maturation might play a role in the recovery process. The effects of reversion on the fatty acid (FA) composition and dopaminergic neurotransmission were studied in brain regions known to be affected by such deficiency (i.e., the prefrontal cortex and nucleus accumbens) in 2-month-old animals. Dopamine release under pharmacological stimulation was studied using a dual-probe microdialysis method. Vesicular monoamine transporters were studied using quantitative autoradiography. The reversal diet, with adequate levels of n-6 and n-3 polyunsaturated fatty acids (PUFAs), was given to deficient rats at different stages of development (0, 7, 14, or 21 days of age). The results showed that when given during the lactating period, this diet was able to restore both the FA composition of brain membranes and the parameters of dopaminergic neurotransmission studied. However, when given from weaning, it allowed partial recovery of biochemical parameters but no recovery of neurochemical factors. The occurrence of profound n-3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions.     

Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat

We explored the effects of chronic alpha-linolenic acid dietary deficiency on serotoninergic neurotransmission. In vivo synaptic serotonin (5-HT) levels were studied in basal and pharmacologically stimulated conditions using intracerebral microdialysis in the hippocampus of awake 2-month-old rats. We also studied the effects of reversion of the deficient diet on fatty acid composition and serotoninergic neurotransmission. A balanced (control) diet was supplied to deficient rats at different stages of development, i.e. from birth, 7, 14 or 21 days of age. We demonstrated that chronic n-3 polyunsaturated fatty acid dietary deficiency induced changes in the synaptic levels of 5-HT both in basal conditions and after pharmacological stimulation with fenfluramine. Higher levels of basal 5-HT release and lower levels of 5-HT-stimulated release were found in deficient than in control rats. These neurochemical modifications were reversed by supply of the balanced diet provided at birth or during the first 2 weeks of life through the maternal milk, whereas they persisted if the balanced diet was given from weaning (at 3 weeks of age). This suggests that provision of essential fatty acids is durably able to affect brain function and that this is related to the developmental stage during which the deficiency occurs.