Perinatal undernourishment provokes long-lasting alterations of clusterin and fumarate hydratase expression in the rat nucleus accumbens

Abstract

Perinatal malnutrition seems to provoke important neurochemical alterations in the brain that lead to higher vulnerability to develop neuropsychiatric disorders in the adulthood. In this work we have examined the persistence and reversibility of the changes induced by perinatal undernourishment on the expression of fumarate hydratase in the rat nucleus accumbens, bearing in mind that this expression has been previously linked with addictive disorders. Clusterin, a multifunctional protein known to be neuroprotective and possibly related to addiction in humans, was studied in parallel.Female rats under severe restriction of food during gestation, lactation and 5 months of postnatal life showed a marked upregulation of both clusterin and fumarate hydratase in the mitochondrial fraction of the nucleus accumbens, as quantified by western blot. In the case of clusterin, this upreglation was also observed in the cytosolic fraction of the nucleus accumbens. When animals were undernourished only during gestation and lactation but then switched to normal chow upon weaning, the two proteins appeared downregulated with respect to controls. The results are consistent with the idea that perinatal malnutrition provokes marked changes of brain neurochemistry that are not fully corrected by the rehabilitation of normal feeding and could be linked to behavioural disturbances in the adulthood, i.e. increased vulnerability to addiction.