Recently, Professor Xiangrong Zhang's research team at the Affiliated Brain Hospital of Nanjing Medical University (NMU) published an article in the internationally renowned journal Molecular Psychiatry, titled "Selective magnetic stimulation downregulates the GABAA receptor ε subunit in the left prelimbic cortex to alleviate schizophrenia-like behaviors in mice".
In this study, the team applied a superparamagnetic iron oxide nanoparticle (SPIO)-mediated combined magnetic stimulation system treatment (c-MSST) in a mouse model of schizophrenia. For the first time, they achieved efficient and precise activation of the prelimbic cortex (PrL) and identified that the GABAA receptor ε subunit (GABRE)—a ligand-gated chloride ion channel—as the core molecular mechanism by which magnetic stimulation alleviates schizophrenia-like behaviors in mice. The findings provide new strategies and potential targets for the physical treatment of schizophrenia.
This study represents the first successful application of the c-MSST intervention system, achieving precise magnetic stimulation of the PrL—a key brain region in schizophrenia.The team innovatively reveals the regulatory mechanism of the GABAA receptor ε subunit (GABRE) as a core molecular target: c-MSST upregulates the p62/SQSTM1 protein, which sequesters GABARAP family molecules, thereby reducing the membrane expression of GABRE. This process reverses MK-801-induced synaptic plasticity impairments and ultimately ameliorates schizophrenia-like behaviors. Research on schizophrenia model mice further demonstrates that c-MSST targeted intervention in the left PrL reverses social, cognitive, and motor deficits, producing effects comparable to those of the classical drug clozapine. This provides a novel physical intervention strategy for schizophrenia.
This technological breakthrough overcomes the limitations of traditional repetitive transcranial magnetic stimulation (rTMS), which faces challenges in achieving precise targeting of specific brain regions and lacks clear mechanistic understanding. Based on clinically applicable SPIO nanoparticles, the developed approach demonstrates high targeting precision, reversible modulation, and excellent biosafety. The study elucidates the neurobiological mechanism by which magnetic stimulation improves schizophrenia-like behaviors via the GABRE-p62/SQSTM1 axis. The "precisely targeted modulation" capability of c-MSST establishes a feasible technical paradigm for both mechanistic studies and therapeutic applications in psychiatric disorders such as schizophrenia, depression, and autism, showing promising clinical translation potential.
Professor Xiangrong Zhang from the Affiliated Brain Hospital of NMU and Professor Zhijun Zhang from Zhongda Hospital Affiliated to Southeast University served as co-corresponding authors. Graduate students Yunshan Hu, Zixu Wang, Jin Fang, and Shaotong Zhang from Professor Xiangrong Zhang's group are co-first authors. This research was supported by the National Natural Science Foundation of China and the Key Social Development Project of the Jiangsu Provincial Department of Science and Technology.
Original article: https://doi.org/10.1038/s41380-025-03267-8.
(Drafted and translated by Professor Xiangrong Zhang’s research team; translation revised by Zhang Bei)
