'Rejuvenation' protects neurons in mouse models of Parkinson's disease

C. Savio Chan, Jaime N. Guzman, Ema Ilijic, Jeff N. Mercer, Caroline Rick, Tatiana Tkatch, Gloria E. Meredith, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

591 Scopus citations

Abstract

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 Cav1.3 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 Cav1.3 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.

Original languageEnglish (US)
Pages (from-to)1081-1086
Number of pages6
JournalNature
Volume447
Issue number7148
DOIs
StatePublished - Jun 28 2007

ASJC Scopus subject areas

  • General

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