title: Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase.
abstract: Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging-related neurodegenerative diseases, such as Parkinson's disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, we studied LC neurons using electrophysiological and optical approaches in ex vivo mouse brain slices. We found that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca(2+) concentration that were attributable to the opening of L-type Ca(2+) channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide increased the spike rate but differentially affected mitochondrial oxidant stress. Oxidant stress was also increased in an animal model of PD. Thus, our results point to activity-dependent Ca(2+) entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons.
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Sanchez-Padilla
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Jaime N
authors.initials: JN
authors.lastname: Guzman
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Ema
authors.initials: E
authors.lastname: Ilijic
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Jyothisri
authors.initials: J
authors.lastname: Kondapalli
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Galtieri
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schieber
authors.affiliation: Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wokosin
authors.affiliation: Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Schumacker
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D003712:Dendrites / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D008125:Locus Coeruleus / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D019001:Nitric Oxide Synthase