Moreover, vitamin A metabolism is essential to maintain striatal function and for adult hippocampal neurogenesis, which seems to be regulated, at least in part, by retinoids (Valdenaire et al., 1998, Zetterström

et al., 1999, McCaffery and Dräger, 1994, Samad et al., 1997, Krezel et al., 1998, Takahashi et al., 1999 and Wang and Liu, 2005). Additionally, the hippocampus is also involved in mood disorders, such as anxiety and depression, and vitamin A is also known to participate in locomotory and exploratory behavior (Bannerman et al., 2003, Bannerman et al., 2004, Deacon and Rawlins, 2005 and File et al., 2000). Therefore, based on previous reports indicating a prooxidant role of vitamin A in a variety of PFT�� nmr experimental models, we have decided to investigate in the present work if the vitamin A supplementation is also able to exert its described prooxidant effects in maternal and offspring rat striatum and hippocampus. Additionally, behavioral parameters evaluation was also targeted. No treatment-related clinical symptoms of toxicity were found in mothers throughout the treatment period. One of the mothers at 12,500 IU/kg/day EPZ015666 ic50 was euthanized on lactation day 4 because it became moribund. Their pups died due to deterioration of maternal condition. The examination of the moribund female and her litter showed no treatment-related

abnormality. No gross malformations were Urocanase observed in pups at post natal day (PND) 0. Incidences of gross lesions were not found during necropsy in dams and pups of the retinyl palmitate-treated groups. Body weight gain in gestation or lactation, gestation length, delivery index, the number of pups delivered, the number of implants and the sex ratio of the litters in retinyl palmitate-treated groups showed no treatment-related changes (Table 1). During nursing, the pups exhibited no treatment-related clinical symptoms.

Litter data revealed that the viability index on PND7 decreased slightly in the 12,500 IU/kg/day group, although no treatment-related reduction in body weights was observed. This was due to the loss of a whole litter as described before. Offspring of retinyl palmitate treated dams showed no significant alteration in the frequency of correct and incorrect performance on homing test in PND5 and PND10 (Table 2). On the other hand, the time spent over the homing area in offspring of treated dams on PND5 increased at all doses when compared to offspring of control dams (according to two-way ANOVA the exposure to retinyl palmitate affect the result, F[3,48] = 24.62, p < 0.0001) (Fig. 1A). However, on PND10 there was no difference between male offspring from retinyl palmitate treated dams and control dams; but, in female offspring palmitate supplementation spent less time over the homing area at 25,000 IU/kg/day (F[3,48] = 5.342, p = 0.0029) (Fig. 1B).