Hagar Moshe1, Ram Gal1, Noam Barnea-Ygael1, Tatiana Gulevsky1, Uri Alyagon1, Abraham Zangen2. 1. Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. 2. Department of Life Sciences and the Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address: azangen@bgu.ac.il.
Abstract
BACKGROUND: Approximately one third of all major depression patients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this Depressive Rat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors. OBJECTIVE: To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats. METHODS: SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in human patients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements. RESULTS: SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions. CONCLUSIONS: Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects.
BACKGROUND: Approximately one third of all major depressionpatients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this DepressiveRat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors. OBJECTIVE: To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats. METHODS: SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in humanpatients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements. RESULTS: SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions. CONCLUSIONS: Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects.
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Authors: Simone Rossi; Andrea Antal; Sven Bestmann; Marom Bikson; Carmen Brewer; Jürgen Brockmöller; Linda L Carpenter; Massimo Cincotta; Robert Chen; Jeff D Daskalakis; Vincenzo Di Lazzaro; Michael D Fox; Mark S George; Donald Gilbert; Vasilios K Kimiskidis; Giacomo Koch; Risto J Ilmoniemi; Jean Pascal Lefaucheur; Letizia Leocani; Sarah H Lisanby; Carlo Miniussi; Frank Padberg; Alvaro Pascual-Leone; Walter Paulus; Angel V Peterchev; Angelo Quartarone; Alexander Rotenberg; John Rothwell; Paolo M Rossini; Emiliano Santarnecchi; Mouhsin M Shafi; Hartwig R Siebner; Yoshikatzu Ugawa; Eric M Wassermann; Abraham Zangen; Ulf Ziemann; Mark Hallett Journal: Clin Neurophysiol Date: 2020-10-24 Impact factor: 4.861