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dc.contributor.authorFuller, Brian F.
dc.contributor.authorFox, Michael A.
dc.description.abstractBackground: Environmental tobacco smoke (ETS) exposure is linked to developmental deficits and disorders with known cerebellar involvement. However, direct biological effects and underlying neurochemical mechanisms remain unclear. Objectives: We sought to identify and evaluate underlying neurochemical change in the rat cerebellum with ETS exposure during critical period development. Methods: We exposed rats to daily ETS (300, 100, and 0 μg/m3 total suspended particulate) from postnatal day 8 (PD8) to PD23 and then assayed the response at the behavioral, neuroproteomic, and cellular levels. Results: Postnatal ETS exposure induced heightened locomotor response in a novel environment on par initially with amphetamine stimulation. The cerebellar mitochondrial subproteome was significantly perturbed in the ETS-exposed rats. Findings revealed a dose-dependent up-regulation of aerobic processes through the modification and increased translocation of Hk1 to the mitochondrion with corresponding heightened ATP synthase expression. ETS exposure also induced a dose-dependent increase in total Dnm1l mitochondrial fission factor; although more active membrane-bound Dnm1l was found at the lower dose. Dnm1l activation was associated with greater mitochondrial staining, particularly in the molecular layer, which was independent of stress-induced Bcl-2 family dynamics. Further, electron microscopy associated Dnm1l-mediated mitochondrial fission with increased biogenesis, rather than fragmentation. Conclusions: The critical postnatal period of cerebellar development is vulnerable to the effects of ETS exposure, resulting in altered behavior. The biological effect of ETS is underlain in part by a Dnm1l-mediated mitochondrial energetic response at a time of normally tight control. These findings represent a novel mechanism by which environmental exposure can impact neurodevelopment and function.
dc.publisherNational Institute of Environmental Health Sciences
dc.rightsCC0 1.0 Universal
dc.subjectattention deficit/hyperactivity disorder
dc.subjectcarbohydrate metabolism
dc.subjectenvironmental tobacco smoke
dc.subjectmitochondrial biogenesis
dc.subjectmitochondrial energetics
dc.subjectsecondhand smoke
dc.subjectsystems biology
dc.titleExposure of Rats to Environmental Tobacco Smoke during Cerebellar Development Alters Behavior and Perturbs Mitochondrial Energetics
dc.title.serialEnvironmental Health Perspectives

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CC0 1.0 Universal
License: CC0 1.0 Universal