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Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Ppublish 24 citations

PubMed: 35834882 DOI: 10.1016/j.psyneuen.2022.105852

Dynamic behavior of cell-free mitochondrial DNA in human saliva.

Psychoneuroendocrinology 143:105852

Authors: Caroline Trumpff, Shannon Rausser, Rachel Haahr, Kalpita R Karan, Gilles Gouspillou, Eli Puterman, Clemens Kirschbaum, Martin Picard

Affiliations

  • Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, USA.
  • Département des Sciences de l'Activité Physique, Faculté des Sciences, Université du Québec à Montréal (UQAM), Montreal, Québec, Canada.
  • School of Kinesiology, University of British Columbia, Vancouver, Canada.
  • Department of Psychology, TU Dresden, Germany.
  • Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, USA; Department of Neurology, H. Houston Merritt Center, Columbia University Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, USA; New York State Psychiatric Institute, New York, USA.

Abstract

Mitochondria contain their own genome that can be released in multiple biofluids such as blood and cerebrospinal fluid, as cell-free mitochondrial DNA (cf-mtDNA). In clinical studies, blood cf-mtDNA predicts mortality and higher cf-mtDNA levels are associated with mental and physical stress. However, the dynamics of cf-mtDNA has not been defined, and whether it can be measured non-invasively like other neuroendocrine markers in saliva has not been examined. Here we report cf-mtDNA in human saliva and establish its natural within-person dynamic behavior across multiple weeks. In a small proof-of-principle cohort of healthy adults, we first develop an approach to rapidly quantify salivary cf-mtDNA without DNA isolation, and demonstrate the existence of salivary cf-mtDNA. We then deploy this approach to perform an intensive repeated-measures analysis of two healthy men studied at 4 daily timepoints over 53-60 consecutive days (n = 212-220 observations each) with parallel measures of steroid hormones, self-reported daily mood, and health-related behaviors. Salivary cf-mtDNA exhibited a robust awakening response reaching up to two orders of magnitude 30-45 min after awakening, varied from day-to-day, and moderately correlated with the cortisol awakening response. In exploratory analyses, no consistent association with self-reported daily mood/health-related behaviors were found, although this requires further examination in future studies. Dynamic variation in cf-mtDNA was inversely related with salivary interleukin 6 (IL-6), inconsistent with a pro-inflammatory effect of salivary cf-mtDNA. The highly dynamic behavior of salivary cf-mtDNA opens the door to non-invasive studies examining the relevance of mtDNA signaling in relation to human health.

MeSH

Endocrinology, Cells, Blood, Interleukin-6, Dna, Mitochondrial, Psychiatry

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