Earlier studies showed that oral administration of green tea or caffeine to SKH-1 mice inhibited ultraviolet B light (UVB)-induced skin carcinogenesis, decreased dermal fat thickness and increased locomotor activity. In the present study, the effects of voluntary running wheel exercise on thickness of dermal fat as well as on UVB-induced tumorigenesis in SKH-1 mice were studied in UVB-initiated high-risk and UVB-induced complete carcinogenesis models. In the high-risk model, animals were exposed to UVB (30 mJ/cm(2)) 3 times/week for 16 weeks. For 14 weeks subsequent to UVB exposure, half of the animals had access to running wheels in their cages whereas the other half did not. In the complete carcinogenesis model, animals were exposed to UVB (30 mJ/cm(2)) 2 times/week for 33 weeks. From the beginning, half of the animals had access to running wheels whereas the other half did not. At the conclusion of each study, body weights were not different between groups, although animals with running wheels consumed significantly more food and water than animals without running wheels. In addition, animals with running wheels had decreases in parametrial fat pad weight and thickness of the dermal fat layer. In both UVB-initiated high-risk and complete carcinogenesis models, voluntary running wheel exercise delayed the appearance of tumors, decreased the number of tumors per mouse and decreased tumor volume per mouse. Histopathology studies revealed that running wheel exercise decreased the number of non-malignant tumors (primarily keratoacanthomas) by 34% and total tumors per mouse by 32% in both models, and running wheel exercise decreased the formation of squamous cell carcinomas in the UVB-induced complete carcinogenesis model by 27%. In addition, the size of keratoacanthomas and squamous cell carcinomas were decreased substantially in both models. The effects described here indicate that voluntary running wheel exercise inhibits UVB-induced skin tumorigenesis and may also inhibit tumor growth.

Progress in Parkinson’s disease (PD) research and therapeutic development is hindered by many challenges, including a need for robust preclinical animal models. Limited availability of these tools is due to technical hurdles, patent issues, licensing restrictions and the high costs associated with generating and distributing these animal models. Furthermore, the lack of standardization of phenotypic characterization and use of varying methodologies has made it difficult to compare outcome measures across laboratories. In response, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) is directly sponsoring the generation, characterization and distribution of preclinical rodent models, enabling increased access to these crucial tools in order to accelerate PD research. To date, MJFF has initiated and funded the generation of 30 different models, which include transgenic or knockout models of PD-relevant genes such as Park1 (also known as Park4 and SNCA), Park8 (LRRK2), Park7 (DJ-1), Park6 (PINK1), Park2 (Parkin), VPS35, EiF4G1 and GBA. The phenotypic characterization of these animals is performed in a uniform and streamlined manner at independent contract research organizations. Finally, MJFF created a central repository at The Jackson Laboratory (JAX) that houses both non-MJFF and MJFF-generated preclinical animal models. Funding from MJFF, which subsidizes the costs involved in transfer, rederivation and colony expansion, has directly resulted in over 2500 rodents being distributed to the PD community for research use.

Glial cell line-derived neurotrophic factor (GDNF) has been shown to be neuroprotective in animal models of the dopamine deficiency in Parkinson's disease. To examine the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in this process, we infused a single dose of GDNF into the striatum of mice and analyzed the effect on ERK1/2 by immunohistochemistry and Western blot analysis. GDNF caused an increase in the phosphorylation of ERK1/2 both in the striatum and in tyrosine hydroxylase-positive neurons in the substantia nigra. In the striatum, the increase in ERK1/2 phosphorylation was evident by 3 hr and persisted for at least 7 days, whereas, in the substantia nigra, an increase in phosphorylated ERK1/2 was first evident at 24 hr and persisted for at least 7 days. The increase in phosphorylated ERK1/2 was maximal at 0.45 microg GDNF at the time points examined. GDNF also protected dopamine terminals against the loss of tyrosine hydroxylase immunoreactivity normally associated with the intrastriatal administration of 6-hydroxydopamine (0.5 microg/0.5 microl). However, this was observed only at a much higher dose of GDNF, 4.5 microg. Thus, our results suggest that the ability of GDNF to protect dopamine neurons cannot be explained solely in terms of its influence on ERK1/2 and that the role of other signaling pathways should be explored.

This study explores how American Indians use interest group strategies to block federal legislation. Unlike other disadvantaged groups, who have influenced public policymaking through descriptive representation, American Indians have turned to interest group strategies to protect their interests in Congress. Using original data collected from American Indian testimony at congressional hearings on 266 bills during five Congresses, this study tests interest group hypotheses about how and when active opposition affects bill enactment. It finds that American Indians can block federal legislation harmful to their interests when they unify against a bill and that members of Congress frequently respond to American Indian opposition by amending bills to alleviate American Indian concerns.