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. 2025 Mar 15:1851:149459.
doi: 10.1016/j.brainres.2025.149459. Epub 2025 Jan 18.

Combination of rTMS and oxytocin agonist attenuate depression-like behavior after postpartum depression in mice

Nashwa Amin  1 , Azhar B Hussein  2 , Qing Ye  3 , Shijia Chen  4 , Fei Wu  2 , Xia Yuan  2 , Irum Naz Abbasi  2 , Javaria Sundus  2 , Zhiying Hu  5 , Marong Fang  6
Affiliations

Combination of rTMS and oxytocin agonist attenuate depression-like behavior after postpartum depression in mice

Nashwa Amin et al. Brain Res. .

Abstract

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) categorizes postpartum depression (PPD) as a subtype of Major Depressive Disorder (MDD) with peripartum onset, generally arising within the initial trimester following delivery. This acute psychiatric condition is characterized by feelings of worthlessness, insomnia, extreme anxiety, or maternal neglect. Intranasal oxytocin (OT) and transcranial magnetic stimulation (TMS) have the potential to address impaired social cognition; nonetheless, their neuronal underpinnings, along with their safety and efficacy, are little comprehended. This study examines the effects of rTMS stimulation with an oxytocin agonist or antagonist in a PPD model. We employed the maternal separation with early weaning (MSEW) strategy for 21 days to attain our objective. Oxytocin acetate (agonist) and atosiban (antagonist) were administered by injection twice daily for three consecutive days following the model according to the established protocol. A single session of rTMS involved the application of high-frequency stimulation (20 Hz) one hour following the final injection. Behavioral testing and brain collection were conducted 12 h post-rTMS. The results indicated that treatment with OT followed by rTMS stimulation decreased neuronal cell death and microglial activation, meanwhile enhancing synaptic plasticity through the upregulation of PSD95, Synapsin I, and Synaptophysin. Simultaneously, both OT therapy and repetitive transcranial magnetic stimulation demonstrated a significant capacity to alter autophagy activity and astrocyte function. Nonetheless, OTA therapy followed by rTMS did not exhibit the same pattern of outcomes. Our findings indicate that the combination of rTMS stimulation and an oxytocin agonist in a PPD model may mitigate depression-like behavior.

Keywords: Behavioral test; Maternal separation; OTA; Oxytocin; PPD; Paternal separation; rTMS.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.