title: Exposure of rats to environmental tobacco smoke during cerebellar development alters behavior and perturbs mitochondrial energetics.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia 23298-0709, USA.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Fuller
authors.forename: Diego F
authors.initials: DF
authors.lastname: Cortes
authors.forename: Miranda K
authors.initials: MK
authors.lastname: Landis
authors.forename: Hiyab
authors.initials: H
authors.lastname: Yohannes
authors.forename: Hailey E
authors.initials: HE
authors.lastname: Griffin
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Stafflinger
authors.forename: M Scott
authors.initials: MS
authors.lastname: Bowers
authors.forename: Mark H
authors.initials: MH
authors.lastname: Lewis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fox
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Ottens
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D034281:Dynamins / Q000378:metabolism; D004781:Environmental Exposure; D006593:Hexokinase / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D063154:Mitochondrial Dynamics / Q000187:drug effects; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D020543:Proteome / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000393:Air Pollutants; D020543:Proteome; D014028:Tobacco Smoke Pollution; D006593:Hexokinase; D025261:Mitochondrial Proton-Translocating ATPases; C519851:Dnm1l protein, rat; D034281:Dynamins