Abnormal brain function of the rat neonate in a prenatal 5-bromo-2′-deoxyuridine (BrdU)-induced developmental disorder model

Neonatal brain function was investigated in a prenatal BrdU-induced developmental disorder model, which has been reported to exhibit behavioral abnormalities such as locomotor hyperactivity, impaired learning and memory, and lower anxiety in offspring. After 1 h home cage deprivation we observed an increase in the number of c-Fos (neuronal activity marker) immunoreactive cells in several brain regions of the olfactory and stress-related areas in normal neonates at 11 days. Next, pregnant rats were exposed to 50 mg/kg of BrdU from gestation days 9–15, and their offspring at 11 days were home-cage deprived. Compared to vehicle control, the number of c-Fos immunoreactive cells in BrdU group was found to be decreased in the piriform cortex and locus coeruleus, which are known to play an important role in neonatal learning and memory. We also analyzed Pearson product–moment correlation coefficient of the number of c-Fos immunoreactive cells, focusing on the piriform cortex and locus coeruleus versus numerous other brain areas (11 areas including amygdala). Numerous significant correlations were observed in the vehicle control group, however, correlations of the locus coeruleus disappeared in the BrdU group. By observing c-Fos immunoreactivity after home cage deprivation our study uncovers abnormal brain functions as early as postnatal day 11 in this disorder model. Based on these results, we propose a new histological approach for functional characterization of developmental disorder models.

► Home cage deprivation induced c-Fos (neuronal activity marker) in normal pup's brain. ► The c-Fos was induced at olfactory and stress-related areas. ► Correlations among those areas were detected for the c-Fos induction. ► Those correlations disappeared in BrdU-induced developmental disorder model. ► New histological approach for developmental disorder models was proposed.