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.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.

MMP-9-Dependent Serum-Borne Bioactivity Caused by Multiwalled Carbon Nanotube Exposure Induces Vascular Dysfunction via the CD36 Scavenger Receptor

“…Separation was performed with a 150 mm × 75 μm HSS T3 reversed-phase capillary column at 55 °C online with a nanoelectrospray equipped Synapt G2 HDMS tandem mass spectrometer (Waters). Separation and data-independent mass spectrometric analysis with ion mobility was performed as described previously (Fuller et al , 2012; Ottens et al , 2014) with the modifications that gradient elution was performed from 2% to 42% acetonitrile in water (formic-acid modified) and spectra were collected between 200 and 1800 m/z, with a collisionenergy ramp from 32 to 52 eV. All spectra were post-processed employing PLGS ion processing software (Waters).…”

Osteopontin expression in acute immune response mediates hippocampal synaptogenesis and adaptive outcome following cortical brain injury

“…The NOR apparatus consists of a 42 × 42 × 30 cm 3 open field arena under red light illumination (1 lux at mouse height) in a sound-isolated room (Fuller et al, 2012). The NOR task consists of three phases: habituation, familiarization, and testing.…”

Amelioration strategies fail to prevent tobacco smoke effects on neurodifferentiation: Nicotinic receptor blockade, antioxidants, methyl donors

“…However, given the advent of nicotine replacement products for smoking cessation, as well as alternative nicotine delivery devices, it becomes important to distinguish whether the thousands of other components of tobacco smoke also play a role in adverse neurodevelopmental outcomes. A number of animal studies have identified effects of cigarette smoke that, in general, resemble those of nicotine at the biochemical, structural and functional levels (Bruijnzeel et al 2011; Fuller et al 2012; Golub et al 2007; Gospe et al 2009; Lobo Torres et al 2012; Sekizawa et al 2008; Slotkin et al 2006a, b). Nevertheless, these exposure models simply reinforce the resemblance between smoke exposure and the effects of nicotine, rather than distinguishing between them.…”