Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase

Javier Sanchez-Padilla, Jaime N. Guzman, Ema Ilijic, Jyothisri Kondapalli, Daniel J. Galtieri, Ben Yang, Simon Schieber, Wolfgang Oertel, David Wokosin, Paul T. Schumacker, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticle

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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 Ca2+ 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 Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons.

Original languageEnglish (US)
Pages (from-to)832-840
Number of pages9
JournalNature Neuroscience
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 2014

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ASJC Scopus subject areas

  • Neuroscience(all)

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