Exposure of Rats to Environmental Tobacco Smoke during Cerebellar Development Alters Behavior and Perturbs Mitochondrial Energetics

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dc.contributor.authorFuller, Brian F.en
dc.contributor.authorFox, Michael A.en
dc.date.accessioned2018-11-19T18:31:57Zen
dc.date.available2018-11-19T18:31:57Zen
dc.date.issued2012-12en
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.en
dc.identifier.doihttps://doi.org/10.1289/ehp.1104857en
dc.identifier.issue12en
dc.identifier.urihttp://hdl.handle.net/10919/85876en
dc.identifier.volume120en
dc.language.isoen_USen
dc.publisherNational Institute of Environmental Health Sciencesen
dc.rightsCreative Commons CC0 1.0 Universal Public Domain Dedicationen
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/en
dc.subjectattention deficit/hyperactivity disorderen
dc.subjectcarbohydrate metabolismen
dc.subjectcerebellumen
dc.subjectenvironmental tobacco smokeen
dc.subjectmitochondrial biogenesisen
dc.subjectmitochondrial energeticsen
dc.subjectneurodevelopmenten
dc.subjectproteomicsen
dc.subjectsecondhand smokeen
dc.subjectsystems biologyen
dc.titleExposure of Rats to Environmental Tobacco Smoke during Cerebellar Development Alters Behavior and Perturbs Mitochondrial Energeticsen
dc.title.serialEnvironmental Health Perspectivesen
dc.typeArticleen
dc.type.dcmitypetexten

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Destination Area: Adaptive Brain and Behavior (ABB)
Scholarly Works, Fralin Biomedical Research Institute at VTC