Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein

Kathleen J. Griffioen, Sarah M. Rothman, Bruce Ladenheim, Ruiqian Wan, Neil Vranis, Emmette Hutchison, Eitan Okun, Jean Lud Cadet, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Parkinson's disease (PD) patients often exhibit impaired regulation of heart rate by the autonomic nervous system (ANS) that may precede motor symptoms in many cases. Results of autopsy studies suggest that brainstem pathology, including the accumulation of α-synuclein, precedes damage to dopaminergic neurons in the substantia nigra in PD. However, the molecular and cellular mechanisms responsible for the early dysfunction of brainstem autonomic neurons are unknown. Here we report that mice expressing a mutant form of α-synuclein that causes familial PD exhibit aberrant autonomic control of the heart characterized by elevated resting heart rate and an impaired cardiovascular stress response, associated with reduced parasympathetic activity and accumulation of α-synuclein in the brainstem. These ANS abnormalities occur early in the disease process. Adverse effects of α-synuclein on the control of heart rate are exacerbated by a high energy diet and ameliorated by intermittent energy restriction. Our findings establish a mouse model of early dysregulation of brainstem control of the cardiovascular system in PD, and further suggest the potential for energy restriction to attenuate ANS dysfunction, particularly in overweight individuals.

Original languageEnglish (US)
Pages (from-to)928-935
Number of pages8
JournalNeurobiology of Aging
Volume34
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • α-synuclein
  • Acetylcholine
  • ANS
  • BDNF
  • Brainstem
  • Parasympathetic
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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    Griffioen, K. J., Rothman, S. M., Ladenheim, B., Wan, R., Vranis, N., Hutchison, E., Okun, E., Cadet, J. L., & Mattson, M. P. (2013). Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein. Neurobiology of Aging, 34(3), 928-935. https://doi.org/10.1016/j.neurobiolaging.2012.07.008