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Published on: March 4, 2015
Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine (BrdU)-induced developmental
Tetsuo Ogawa1, Makiko Kuwagata, Katsumasa Muneoka
1Department of Anatomy, Showa University, School of Medicine, Tokyo, Japan. t.ogawa@med.showa-u.ac.jp
Insights
Prenatal exposure to BrdU in a rat model disrupts neonatal brain function, indicated by reduced neuronal activity in key areas. This study reveals early functional deficits in developmental disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Animal Models
Background:
- Prenatal exposure to Bromodeoxyuridine (BrdU) can induce developmental disorders in offspring, leading to behavioral abnormalities.
- Neonatal brain function and neuronal activity patterns are critical for normal development and behavior.
Purpose of the Study:
- To investigate the impact of prenatal BrdU exposure on neonatal brain function using a rat model.
- To identify specific alterations in neuronal activity in response to stress in offspring exposed to BrdU during gestation.
Main Methods:
- Utilized a rat model with prenatal BrdU induction (50mg/kg, gestation days 9-15).
- Assessed neuronal activity via c-Fos immunoreactivity in 11-day-old offspring after 1-hour home cage deprivation.
- Analyzed c-Fos expression in olfactory and stress-related brain regions, including the piriform cortex and locus coeruleus.
- Correlated c-Fos expression between brain regions using Pearson product-moment correlation.
Main Results:
- Home cage deprivation increased c-Fos positive cells in normal neonates.
- BrdU-exposed offspring showed decreased c-Fos cells in the piriform cortex and locus coeruleus compared to controls.
- Significant correlations between locus coeruleus and other brain areas observed in controls were absent in the BrdU group.
Conclusions:
- Prenatal BrdU exposure causes functional brain abnormalities as early as postnatal day 11 in rats.
- Altered neuronal activity in the piriform cortex and locus coeruleus suggests impaired learning and memory processing.
- This study proposes a novel histological method for characterizing functional deficits in developmental disorder models.
Abstract:
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 1h 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 50mg/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.
