High-Frequency rTMS can Improve Depressive Symptoms by Promoting Mitochondrial Fusion

Area of Science:

• Neuroscience
• Cell Biology
• Psychiatry

Background:

• Depression is a prevalent disabling mental disorder.
• Repetitive transcranial magnetic stimulation (rTMS) shows efficacy in improving depressive symptoms.
• Mitochondrial quality control (MQC) is implicated in psychiatric disorders, but its link to rTMS mechanisms is unclear.

Purpose of the Study:

• To evaluate the therapeutic effect of rTMS on depression.
• To investigate the relationship between rTMS and mitochondrial quality control.

Main Methods:

• A mouse model of depression was induced using chronic unpredictable mild stress (CUMS).
• Mice were treated with 10 Hz rTMS daily for 4 weeks.
• Depression-like behaviors were assessed using open field, tail suspension, sucrose preference, and forced swimming tests.
• Immunohistochemistry and transmission electron microscopy were used to examine the prefrontal cortex and hippocampus, focusing on mitochondrial morphology and autophagy markers.

Main Results:

• rTMS treatment significantly improved depression-like behaviors in mice.
• Mitochondrial pre-autophagy (LC3 I/II, FIS1) and mitochondrial fusion (NeuN, c-Fos, MFN1) were enhanced in the hippocampus after rTMS treatment.
• These molecular changes correlated with behavioral improvements.

Conclusions:

• rTMS therapy effectively ameliorates depression-like behaviors in a mouse model.
• The therapeutic effects of rTMS are mediated by promoting mitochondrial fusion and enhancing autophagy.
• This study elucidates a key cellular mechanism underlying rTMS treatment for depression.