Parkin-deficient Mice Exhibit Nigrostriatal Deficits but not Loss of Dopaminergic Neurons

Loss-of-function mutations in parkin are the major cause of early-onset familial Parkinson's disease. To investigate the pathogenic mechanism by which loss of parkin function causes Parkinson's disease, we generated a mouse model bearing a germline disruption in parkin. Parkin-/- mice are viable and exhibit grossly normal brain morphology. Quantitative in vivo microdialysis revealed an increase in extracellular dopamine concentration in the striatum of parkin-/- mice. Intracellular recordings of medium-sized striatal spiny neurons showed that greater currents are required to induce synaptic responses, suggesting a reduction in synaptic excitability in the absence of parkin. Furthermore, parkin-/- mice exhibit deficits in behavioral paradigms sensitive to dysfunction of the nigrostriatal pathway. The number of dopaminergic neurons in the substantia nigra of parkin-/- mice, however, is normal up to the age of 24 months, in contrast to the substantial loss of nigral neurons characteristic of Parkinson's disease. Steady-state levels of CDCrel-1, synphilin-1, and α-synuclein, which were identified previously as substrates of the E3 ubiquitin ligase activity of parkin, are unaltered in parkin-/- brains. Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice

Mercury concentrations in blood, brain and muscle tissues of coastal and pelagic birds from northeastern Canada

Mercury (Hg) is a toxic element which has increased in marine environments for more than a century, due largely to anthropogenic activities, and biomagnifies in food chains to harmful levels in some top predators like waterfowl and seabirds. We analysed total mercury (THg) concentrations in blood, brain and muscle tissue from healthy specimens of 13 coastal and pelagic bird species from eastern and northern Canada to provide a baseline on c