Impact of subthalamic nucleus deep brain stimulation at different frequencies on neurogenesis in a rat model of Parkinson's disease
Zheng Wu,
Zhiwei Ren,
Runshi Gao,
Ke Sun,
Fangling Sun,
Tingting Liu,
Songyang Zheng,
Wen Wang,
Guojun Zhang
Affiliations
Zheng Wu
Department of Functional Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China
Zhiwei Ren
Department of Functional Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China
Runshi Gao
Department of Functional Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, China; Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing, China
Ke Sun
Functional Neurosurgery Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
Fangling Sun
Department of Experimental Animal Laboratory, Xuan-Wu Hospital of Capital Medical University, Beijing, China
Tingting Liu
Department of Experimental Animal Laboratory, Xuan-Wu Hospital of Capital Medical University, Beijing, China
Songyang Zheng
Department of Experimental Animal Laboratory, Xuan-Wu Hospital of Capital Medical University, Beijing, China
Wen Wang
Department of Experimental Animal Laboratory, Xuan-Wu Hospital of Capital Medical University, Beijing, China; Corresponding author. Department of Experimental Animal Laboratory, Xuanwu Hospital, Capital Medical University, No.45 Changchun Street, Xicheng District, Beijing, 10053, China.
Guojun Zhang
Functional Neurosurgery Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; Corresponding author. Functional Neurosurgery Department, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No.56 Nanlishi Road, Xicheng District, Beijing 100045, China.
Neurogenesis, play a vital role in neuronal plasticity of adult mammalian brains, and its dysregulation is present in the pathophysiology of Parkinson's disease (PD). While subthalamic nucleus deep brain stimulation (STN-DBS) at various frequencies has been proven effective in alleviating PD symptoms, its influence on neurogenesis remains unclear. This study aimed to investigate the effects of 1-week electrical stimulation at frequencies of 60Hz, 130Hz, and 180Hz on neurogenesis in the subventricular zone (SVZ) of PD rats. A hemiparkinsonian rat model was established using 6-hydroxydopamine and categorized into six groups: control, PD, sham stimulation, 60Hz stimulation, 130Hz stimulation, and 180Hz stimulation. Motor function was assessed using the open field test and rotarod test after one week of STN-DBS at different frequencies. Tyrosine hydroxylase (TH) expression in brain tissue was analyzed via Western blot and immunohistochemistry. Immunofluorescence analysis was conducted to evaluate the expression of BrdU/Sox2, BrdU/GFAP, Ki67/GFAP, and BrdU/DCX in bilateral SVZ and the rostral migratory stream (RMS). Our findings revealed that high-frequency STN-DBS improved motor function. Specifically, stimulation at 130Hz increased dopaminergic neuron survival in the PD rat model, while significantly enhancing the proliferation of neural stem cells (NSCs) and neuroblasts in bilateral SVZ. Moreover, this stimulation effectively facilitated the generation of new NSCs in the ipsilateral RMS and triggered the emergence of fresh neuroblasts in bilateral RMS, with notable presence within the lesioned striatum. Conversely, electrical stimulation at 60Hz and 180Hz did not exhibit comparable effects. The observed promotion of neurogenesis in PD rats following STN-DBS provides valuable insights into the mechanistic basis of this therapeutic approach for PD.
