N-methyl-N-nitrosourea-induced cerebellar hypoplasia in rats: Effect of arachidonic acid supplementation during the gestational, lactational and post-weaning periods

Abstract

Arachidonic acid (AA) is a fatty acid that is important for visual and brain development and is commonly added as a functional food ingredient to commercial infant formulas worldwide. However, few studies have examined whether AA supplementation during neonatal life has an effect on neuronal abnormalities. In the present study, the effect of dietary AA supplementation in dams during gestation and lactation was investigated by examining N-methyl-N-nitrosourea (MNU)-induced cerebellar hypoplasia in young Lewis rats. Dams were fed a 2.0% AA diet or a basal diet (<0.01% AA). At birth (postnatal day 0), male and female pups received a single intraperitoneal injection of 35 mg/kg MNU or vehicle. Brain weights were measured and a morphological analysis of macroscopic and histological specimens was conducted after 7, 14, 21, 28 and 60 days. Irrespective of whether the rats had been fed an AA diet, the brain weights of the MNU-treated rats, particularly the weights of the cerebellum, were decreased compared with those of the MNU-untreated rats from the 14th day following the MNU injection. Macroscopic reductions in the cerebellar length and/or width and histologically observed reductions in cerebellar vertex height and/or cortex width were also detected in the MNU-treated rats, irrespective of whether the rats had been fed with AA. Histopathologically, the MNU-treated rats (irrespective of AA supplementation) exhibited disorganization of the cerebellar cortex and disarrangement of the cortical layers (loss and/or disturbance of the molecular, Purkinje and granular cell layers). There were no significant differences in any parameters among the MNU-treated rats, irrespective of whether the rats had been fed an AA diet. In conclusion, an AA-rich diet for dams during gestation and lactation did not modify MNU-induced cerebellar hypoplasia in their offspring.