'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.
Chan
C Savio
CS
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Guzman
Jaime N
JN
Ilijic
Ema
E
Mercer
Jeff N
JN
Rick
Caroline
C
Tkatch
Tatiana
T
Meredith
Gloria E
GE
Surmeier
D James
DJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D004553:Electric Conductivity; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D012402:Rotenone / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D000978:Antiparkinson Agents; C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D012402:Rotenone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002118:Calcium; D004298:Dopamine