title: Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine (BrdU)-induced developmental disorder model.
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.
authors.affiliation: Department of Anatomy, Showa University, School of Medicine, Tokyo, Japan. t.ogawa@med.showa-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Kuwagata
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Chizu
authors.initials: C
authors.lastname: Wakai
authors.forename: Mika
authors.initials: M
authors.lastname: Senuma
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kubo
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000633:toxicity*; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D001973:Bromodeoxyuridine / Q000633:toxicity; D002658:Developmental Disabilities / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012934:Social Isolation
chemical_list: D000963:Antimetabolites; D016760:Proto-Oncogene Proteins c-fos; D001973:Bromodeoxyuridine