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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 ?-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, ?-amino-n-butyric acid and 3-methylhistidine may have utility as biomarkers to objectively monitor the response to rTMS treatment of depression.

SUBMITTER: Heath A

PROVIDER: S-EPMC6033856 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms.

Heath Alesha A Lindberg Daniel R DR Makowiecki Kalina K Gray Avalon A Asp Anders J AJ Rodger Jennifer J Choi Doo-Sup DS Croarkin Paul E PE

Translational psychiatry 20180705 1

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 comp ...[more]

PMID: 29976924

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Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms.

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Medium- and high-intensity rTMS reduces psychomotor agitation with distinct neurobiologic mechanisms.

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