'Rejuvenation' protects neurons in mouse models of Parkinson's disease.
Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease.
Pubmed ID: 17558391 RIS Download
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine | Aging | Animals | Antiparkinson Agents | Calcium | Calcium Channels, L-Type | Dendrites | Disease Models, Animal | Disease Progression | Dopamine | Electric Conductivity | Gene Deletion | Male | Mice | Mice, Inbred C57BL | Mitochondria | Models, Neurological | Neurons | Parkinson Disease | Rotenone | Substantia Nigra