ABSTRACT
Polybrominated diphenyl ethers (PBDEs) are widely used commercial flame retardants that are accumulating in the environment. PBDEs may interfere with the development of key biological systems, thus leaving children vulnerable to functional impairments in adulthood. There is a growing literature of animal studies that show subtle changes in motor and cognitive function following acute or repeated perinatal exposure to PBDEs. 2,2',4,4'-Brominated diphenyl ether (BDE 47), a very stable PBDE congener, has been shown to accumulate in humans, perhaps as a breakdown product of other PBDEs. The current study examined developmental milestones in male C57BL/6 mice exposed to a single oral dose of BDE 47 (0, 1, 10, or 30 mg/kg) on postnatal day (PND) 10. Behavioral endpoints assessing sensory and motor maturation were examined on PNDs 12, 14, 16, 18, 32, and 88. Motor activity was also examined at 2 and 4 months in a separate group of mice. BDE 47 exposure (particularly the highest dose) significantly increased body weight on PND 47 and thereafter. There was altered ontogeny in a few measures of neuromotor development; however, other developmental milestones and sensory responses were not altered. Motor activity was altered at both 2 and 4 months, with BDE 47-treated mice (all dose groups) displaying pronounced hyperactivity at 4 months. These data indicate that acute exposure to BDE 47 during postnatal development may produce subtle changes in the development of neuromotor systems that may alter adult behavior.
Subject(s)
Motor Activity/drug effects , Motor Neurons/drug effects , Polybrominated Biphenyls/toxicity , Aging/physiology , Animals , Animals, Newborn , Behavior, Animal/drug effects , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Halogenated Diphenyl Ethers , Male , Mice , Mice, Inbred C57BL , Neurons, Afferent/drug effects , PregnancyABSTRACT
Elements within the first cytoplasmic loop of voltage-gated sodium channels have been implicated in regulating channel function. We have examined the role of alternative splicing within the first cytoplasmic loop of the Drosophila sodium channel gene para in regulating sodium current expression, using single-cell RT-PCR. In addition to a previously described exon (a), we identified a second exon in this region, designated exon i. Alternative splicing of exons a and i results in the expression of four para transcripts that are present individually or in combination within single neurons. Analysis of sodium current density and the pattern of para mRNA expression suggested that the presence of exon a was necessary though not sufficient for expression of sodium currents in cultured embryonic neurons. A similar pattern of alternative splicing of para mRNA was also evident in RNA isolated from whole embryos. Combined with our observation that the patterns of alternative splicing of para mRNA change during development, these findings suggest that neuronal sodium current expression in vivo, is also modulated by alternative splicing.
