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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.

Basic and Clinical Neuroscience
|June 1, 2026
PubMed
Summary

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This summary is machine-generated.

Maternal separation (MS) in rats induced depressive-like behavior and cognitive deficits. Intermittent theta burst stimulation (iTBS) effectively improved these outcomes, reducing anxiety and enhancing memory. This study highlights iTBS as a potential therapy for stress-induced mental health issues.

Area of Science:

  • Neuroscience
  • Behavioral Science
  • Pharmacology

Background:

  • Early life stress, exemplified by maternal separation (MS), is a significant risk factor for developing mental health disorders, including depression and cognitive impairment later in life.
  • Intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS), is an emerging non-invasive brain stimulation technique with therapeutic potential.
  • The efficacy of iTBS in mitigating the long-term behavioral and cognitive consequences of early life stress, specifically in the context of MS-induced models, remains largely unexplored.

Purpose of the Study:

  • To investigate the therapeutic potential of an iTBS protocol in an established rodent model of maternal separation (MS).
  • To evaluate the effects of iTBS on depressive-like behavior, anxiety-like behavior, and cognitive deficits induced by MS in male rats.
  • To examine the impact of iTBS on key neurochemical markers associated with oxidative stress, inflammation, and neurotrophic factors in the hippocampus.
Keywords:
DepressionIntermittent theta burst stimulation (iTBS)Maternal separation (MS)Oxidative stress

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Main Methods:

  • Depression and anxiety models were induced in male rats via maternal separation (MS) from postnatal day (PND) 2 to PND 20.
  • Following MS, rats received daily iTBS treatment for 10 consecutive days starting at PND 30.
  • Behavioral assessments including the Barnes maze, open field test (OFT), elevated plus maze (EPM), and forced swim test (FST) were conducted at PND 40. Biochemical analyses of hippocampal tissue were performed at PND 50.

Main Results:

  • iTBS treatment significantly ameliorated MS-induced spatial memory deficits, reduced anxiety-like behaviors in the EPM, and decreased depressive-like behaviors observed in the FST.
  • Biochemical analyses revealed that iTBS significantly reduced markers of oxidative stress (SOD, ROS, MDA, CAT, GSH), inflammation (TNFα), and BACE1 levels in the hippocampus.
  • Furthermore, iTBS treatment led to a significant increase in the levels of brain-derived neurotrophic factor (BDNF) in the hippocampus.

Conclusions:

  • The findings suggest that the iTBS protocol demonstrates significant therapeutic efficacy in reversing behavioral and cognitive impairments associated with maternal separation-induced stress.
  • iTBS exerts its beneficial effects by modulating neuroinflammation, oxidative stress, and promoting neurotrophic support, as indicated by changes in TNFα, oxidative stress markers, BACE1, and BDNF.
  • This study supports the potential of iTBS as a promising non-invasive neuromodulatory strategy for treating mental health conditions linked to early life stress.