Background: Unhealthy pregnant women living in underdeveloped regions are usually treated by traditional healers, inadvertent of the potential toxic effects of plantderivative substances. Thus, we investigated whether exposure to a hydroalcoholic extract of bark and seed of Libidibia ferrea during pregnancy results in fetotoxicity and maternal toxicity. The main constituents of both extracts were analyzed by High Performance Liquid Chromatography (HPLC). Methods: Pregnant rats were divided into three groups: control (C), group exposed to extract of bark (Lfb-1.0 g/kg/day), and group exposed to extract of the seed (Lfs-1.0 g/kg/day). Biochemical parameters, reproductive capacity, morphological effects in the offspring were analyzed. Results: HPLC fingerprint confirmed the presence of ellagic in both bark and seed extracts, and the absence of detectable concentrations of gallic and catechin.Fetuses exposed to L. ferrea extracts presented shorter mean lengths for head and body sections when compared to those in C and exhibited visceral and skeletal anomalies. Pregnant rats exposed to Lfs extracts show alterations in serum creatinine levels and yield amniotic fluid with abnormal biochemical composition. Conclusion: Bark or seed extracts of L. ferrea do not exhibit safety level compatible to be used in the gestational period. K E Y W O R D S fetal development, Libidibia ferrea, maternal exposure, plant extracts, teratogenesis

Previous evidence indicated a potential mechanism that might support the fact that primates exhibit greater neural integration capacity as a result of the activation of different structures of the central nervous system, as compared to rodents. The current study aimed to provide further evidence to confirm previous findings by analyzing the patterns of c-Fos expression in more neocortical structures of rats and marmosets using a more robust quantitative technique and evaluating a larger number of brain areas. Nineteen Wistar rats and 21 marmosets (Callithrix jacchus) were distributed among control groups (animals without injections) and animals injected with pentylenetetrazol (PTZ) and euthanized at different time points after stimulus. Immunohistochemical detection of c-Fos was quantified using unbiased and efficient stereological cell counting in eight neocortical regions. Marmosets had a c-Fos expression that was notably more widely expressed (5× more cells) and longer lasting (up to 3 hr) than rats. c-Fos expression in rats presented similar patterns of expression according to the function of the brain cortical structures (associative, sensorial, and motor functions), which was not observed for marmosets (in which no clear pattern could be drawn, and a more diverse profile emerged). Our results provide evidence that the marmoset brain has a greater neuronal activation after intense stimulation by means of PTZ and a more complex pattern of brain activation. We speculate that these functional differences may contribute for the understanding of the different neuronal processing capacities of the neocortex in these mammals' orders.

Highlights d Spontaneous seizures in APP mice increase DFosB in the dentate gyrus d DFosB binds and recruits HDAC to suppress expression of genes such as c-fos d Blocking DFosB signaling restores gene expression and normalizes memory in APP mice d DFosB's long half-life enables persistent regulation of gene expression

Highlights d Spontaneous seizures in APP mice increase DFosB in the dentate gyrus d DFosB binds and recruits HDAC to suppress expression of genes such as c-fos d Blocking DFosB signaling restores gene expression and normalizes memory in APP mice d DFosB's long half-life enables persistent regulation of gene expression