In a PD mouse model, SNc dendrites are lost (left). But these neurons are protected by a calcium channel blocker (right).


Reverting adult dopamine-secreting neurons to a more youthful state might slow or stop the progression of Parkinson's disease (PD), report Savio Chan, James Surmeier, and colleagues (Northwestern University, Chicago, IL).

The movement defects that characterize PD are caused by the death of dopaminergic neurons in a part of the brain called the substantia nigra pars compacta (SNc). SNc neurons have a pacemaking ability that ensures the regular release of small pulses of dopamine needed to maintain brain function.

Unlike other dopaminergic neurons, those in the SNc depend on calcium channels for pacemaking activity. According to Surmeier, however, mice that lack these calcium channels have no noticeable motor control deficits. His group now shows that the pacemaking activity of these mutant SNc neurons is unaffected.

SNc neurons in the mutant mice carried on pacemaking by instead relying on sodium channels. Sodium channels were normally responsible for pacemaking only in young mice. As the neurons aged, sodium channels took over the pacemaking duties. Neurons from the mice lacking calcium channels thus continued to use the juvenile pacemaking strategy.

The group wondered whether they might revert wild-type adult SNc neurons to a similar juvenile state by simply blocking the calcium channels. Treating SNc neurons with a known calcium channel inhibitor, called isradipine, initially stopped pacemaking activity. After several hours of treatment, however, the pacemaking activity returned, now resembling that of juvenile neurons.

Evidence suggests that rising calcium levels inside SNc neurons might cause cell death in PD. The team found that isradipine reduced the loss of SNc neurons and prevented the development of motor deficits in a mouse model of PD.

Isradipine is a member of a class of drugs called dihydropyridines that are used to treat hypertension and stroke. Retrospective analysis of patient treatment data suggests that dihydropyridines reduce the incidence of PD. The fact the drug is approved for human use means that its efficacy in preventing the progression of PD could be tested immediately.


Chan, C.S., et al.