Precise Magnetic Stimulation of the Paraventricular Nucleus Improves Sociability in a Mouse Model of ASD

Sha Liu1,2 · Quyang Yang1,2 · Pengfei Zhu1,2 · Xuan Liu3  · Qingbo Lu4  · Jie Yang7  · Jingyao Gao7  · Hongbin Han8  · Zhijun Zhang4,6 · Ning Gu5  · Tao Tan7  · Jianfei Sun1,2

1 Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210009, China 

2 State Key Laboratory of Digital Medical Engineering, Southeast University, Nanjing 210096, China 

3 Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing 210009, China 

4 Department of Neurology, Afliated Zhongda Hospital, Research Institution of Neuropsychiatry, School of Medicine, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210009, China 

5 Nanjing Key Laboratory for Cardiovascular Information and Health Engineering Medicine, Institute of Clinical Medicine, Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing 210093, China 

6 Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression, Department of Mental Health and Public Health, Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 

7 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer’s Disease of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Afliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou 325000, China 

8 Department of Radiology, Beijing Key Laboratory of Magnetic Resonance Imaging Devices and Technology, Peking University Third Hospital, Beijing 100191, China

Abstract

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.

Keywords

Superparamagnetic nanodrugs; Deep brain magnetic stimulation; Hypothalamus paraventricular nucleus; Oxytocin; Autism

[Springerlink]