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Intermittent Theta Burst Stimulation Mitigates Depressive-Like behavior in Rats Subjected to Maternal Separation
Gila Pirzad Jahromi1, Masoud Afshari2, Mehrdad Roghani3
1Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Introduction:
Early life stress, such as maternal separation (MS), can lead to serious mental health problems, such as depressive-like behavior in later life. Intermittent theta burst stimulation (iTBS) is a transcranial magnetic stimulation (TMS) protocol. In this study, we sought to determine the effectiveness of the iTBS protocol on depressive-like behavior and cognitive impairment induced by MS in male rats because the therapeutic effect of this protocol on this model remains unknown.
Methods:
To induce depression, we used the MS method from postnatal day (PND) 2 to PND 20 for 4 hours each day. At PND 30, the iTBS treatment began and continued for 10 consecutive days. At PND 40, behavioral tests (Barnes maze, open field test (OFT), elevated plus maze (EPM), and forced swim test [FST]) were conducted. The rats were sacrificed on day 50, with brain tissue removed for biochemical analysis (oxidative stress, tumor necrosis factor alpha [TNFα], brain-derived neurotrophic factor [BDNF], and beta-secretase 1 [BACE1]).
Results:
Based on the results, iTBS significantly improved spatial memory impaired by MS, as evidenced in the Barnes maze, and significantly reduced anxiety-like behavior shown in the EPM and depressive-like behavior demonstrated in the FST. Biochemical analysis showed that iTBS significantly reduced oxidative stress (superoxide dismutase [SOD], reactive oxygen species [ROS], malondialdehyde [MDA], catalase [CAT], and glutathione [GSH]), inflammation (TNFα), and BACE1, but increased BDNF in the hippocampus.
Conclusion:
Taken together, our study suggests that the iTBS protocol may have therapeutic effects on depressive-like behavior and cognitive impairment induced by MS.
Highlights:
MS caused depression, anxiety, and cognitive deficits.iTBS improved behavioral and cognitive outcomes.iTBS reduces inflammation, oxidative stress, and BACE1, but increases BDNF.
Plain Language Summary:
Early life stress can have a long-lasting effect on the brain and mental health. This early life stress can also be used as a model in animals, using maternal separation, to study the effect of this stress on the brain and to look for new therapeutic options. In our study, we induced depression by separating pups from their mothers for certain periods of time, and then we explored whether a protocol of transcranial magnetic stimulation called intermittent theta burst stimulation (iTBS) could reduce depression and other negative effects on the brain or behavior. It is worth mentioning that this method is already used in humans, but the effect of this method on maternal separation-induced depression is underexplored. Rats who received this kind of stimulation for a period of time showed reduced depressive behavior, less anxiety, and improved memory. We also looked for improvement in the brain. Our observations showed that brain damage was reduced with our treatment compared to untreated rats.
