@article{bbaab10148664103814243a375ef34a8,
title = "Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms",
abstract = "Definitive data are lacking on the mechanism of action and biomarkers of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression. Low-intensity rTMS (LI-rTMS) has demonstrated utility in preclinical models of rTMS treatments but the effects of LI-rTMS in murine models of depression are unknown. We examined the behavioral and neurobiologic changes in olfactory bulbectomy (OB) mice with medium-intensity rTMS (MI-rTMS) treatment and fluoxetine hydrochloride. We then compared 10-Hz rTMS sessions for 3 min at intensities (measured at the cortical surface) of 4 mT (LI-rTMS), 50 mT (medium-intensity rTMS [MI-rTMS]), or 1 T (high-intensity rTMS [HI-rTMS]) 5 days per week over 4 weeks in an OB model of agitated depression. Behavioral effects were assessed with forced swim test; neurobiologic effects were assessed with brain levels of 5-hydroxytryptamine, brain-derived neurotrophic factor (BDNF), and neurogenesis. Peripheral metabolomic changes induced by OB and rTMS were monitored through enzyme-linked immunosorbent assay and ultrapressure liquid chromatography-driven targeted metabolomics evaluated with ingenuity pathway analysis (IPA). MI-rTMS and HI-rTMS attenuated psychomotor agitation but only MI-rTMS increased BDNF and neurogenesis levels. HI-rTMS normalized the plasma concentration of α-amino-n-butyric acid and 3-methylhistidine. IPA revealed significant changes in glutamine processing and glutamate signaling in the OB model and following MI-rTMS and HI-rTMS treatment. The present findings suggest that MI-rTMS and HI-rTMS induce differential neurobiologic changes in a mouse model of agitated depression. Further, α-amino-n-butyric acid and 3-methylhistidine may have utility as biomarkers to objectively monitor the response to rTMS treatment of depression.",
author = "Alesha Heath and Lindberg, {Daniel R.} and Kalina Makowiecki and Avalon Gray and Asp, {Anders J.} and Jennifer Rodger and Choi, {Doo Sup} and Croarkin, {Paul E.}",
note = "Funding Information: We thank Sofia Rinaldi and Marissa Penrose-Menz for assistance with animal work, and acknowledge the facilities and scientific and technical expertise of CELLCentral, School of Human Sciences, University of Western Australia. This work was supported by the Mayo Center for Discovery Team Science Award and the Mayo Clinical and Translational Science Award (UT1TR000135) (D.S.-C. and P.E.C.); a University of Western Australia postgraduate award (A.H.); a University of Western Australia Cockell Research Collaboration Award (J.R., D.S.-C., and P.E.C.); a National Health and Medical Research Council Australia Senior Research Fellowship (J.R.); the Neurotrauma Research Program of Western Australia (J.R.); the Ulm Foundation, Mayo Graduate School, and National Institute on Alcohol Abuse and Alcoholism (AA018779) (D.S.-C.); a Brain and Behavior Research Foundation Young Investigator Award (P.E.C.); and the National Institute of Mental Health (K23MH100266 and R01MH113700) (P.E.C.). Funding Information: The content of this report is the sole responsibility of the authors and does not necessarily represent the official views of the US Department of Health and Human Services, the National Institutes of Health, the National Institute of Alcohol Abuse and Alcoholism, the National Institute of Mental Health, University of Western Australia, National Health and Medical Research Council Australia, Neurotrauma Research Program of Western Australia, or the Ulm Foundation. Funding Information: We thank Sofia Rinaldi and Marissa Penrose-Menz for assistance with animal work, and acknowledge the facilities and scientific and technical expertise of CELLCentral, School of Human Sciences, University of Western Australia. This work was supported by the Mayo Center for Discovery Team Science Award and the Mayo Clinical and Translational Science Award (UT1TR000135) (D.S.-C. and P.E.C.); a University of Western Australia postgraduate award (A.H.); a University of Western Australia Cockell Research Collaboration Award (J.R., D.S.- C., and P.E.C.); a National Health and Medical Research Council Australia Senior Research Fellowship (J.R.); the Neurotrauma Research Program of Western Australia (J.R.); the Ulm Foundation, Mayo Graduate School, and National Institute on Alcohol Abuse and Alcoholism (AA018779) (D.S.-C.); a Brain and Behavior Research Foundation Young Investigator Award (P.E.C.); and the National Institute of Mental Health (K23MH100266 and R01MH113700) (P.E.C.). Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41398-018-0129-3",
language = "English (US)",
volume = "8",
journal = "Translational psychiatry",
issn = "2158-3188",
publisher = "Nature Publishing Group",
number = "1",
}