Motor and Cerebellar Effects in Rats Exposed to PCBs and Methylmercury During Early Development

137 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.Polychlorinated biphenyls (PCBs) and methylmercury (MeHg) are found in the same food sources, particularly fish and seafood, and recent studies suggest they may have additive or interactive effects on the nervous system. High doses of MeHg are known to target the cerebellum and impair balance and coordination, but the effects of lower doses were unclear and the effects of PCBs were not well-studied. Therefore, we investigated the effects of developmental PCB and/or MeHg exposure on motor function and cerebellar structure. Female Long-Evans rats were divided into four groups: (1) vehicle controls, (2) PCBs only, (3) MeHg only, and (4) PCB+MeHg. Exposures to PCBs and/or MeHg began 4 weeks prior to breeding and continued to postnatal day (PND) 16. The offspring were weaned on PND21 and tested as adults on three motor tasks---climbing a vertical rope, traversing parallel bars, and crossing a rotating rod. We found no clear deficits on the rope climb or parallel bars following the exposures. However, combined exposure to PCBs and MeHg caused significant increases in the number of slips from the rotating rod that were especially apparent at the highest rpms. Rotating rod deficits can be indicative of cerebellar damage. At high doses MeHg targets the cerebellum causing structural changes. PCBs may also alter cerebellar structure via their effects on thyroid hormones. Therefore, we investigated the effects of combined PCB and MeHg exposure on Purkinje cells (PCs) and cerebellar structure. Golgi-stained PCs were examined in PND21 brains. There were no significant changes in dendritic tree branching area, primary dendrite length, or PC structural abnormalities, which included ectopic PCs. However, exposed male rats did show a marginally significant increase in PC height, suggesting a subtle thyromimetic effect in the cerebellum. Adult brains were collected at the end of motor testing, but there were no exposure-related changes in adult cerebellar weight, PC number, total volume, or layer volumes with the paramedian lobule, which is vital for limb control. These findings suggest that alternative hypotheses for the rotating rod deficit should be examined, including alterations in intracellular calcium signaling within the cerebellum or changes in vestibular system development.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD