High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway
Background High-frequency repetitive transcranial magnetic stimulation (HF rTMS) is a promising non-invasive treatment for Parkinson’s disease (PD) in clinical settings. However, the precise mechanisms are incompletely understood. The proNGF-p75NTR-sortilin signaling pathway is closely associated wi...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2025-07-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/19633.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849421631900876800 |
|---|---|
| author | Rui Zhao Wanqing Du Ke Tian Kunlong Zhang Hua Yuan Fang Gao Xin Kang Xiaolong Sun |
| author_facet | Rui Zhao Wanqing Du Ke Tian Kunlong Zhang Hua Yuan Fang Gao Xin Kang Xiaolong Sun |
| author_sort | Rui Zhao |
| collection | DOAJ |
| description | Background High-frequency repetitive transcranial magnetic stimulation (HF rTMS) is a promising non-invasive treatment for Parkinson’s disease (PD) in clinical settings. However, the precise mechanisms are incompletely understood. The proNGF-p75NTR-sortilin signaling pathway is closely associated with nigrostriatal dopaminergic (DA) neuron degeneration, a hallmark feature of PD. This study aimed to evaluate the neuroprotective efficacy of HF rTMS on the proNGF-p75NTR-sortilin pathway in PD. Methods Using a PD rat model induced by 6-hydroxydopamine (6-OHDA), the rats were randomly divided into two groups: sham rTMS group and HF rTMS group. After a 4 w intervention, the rats’ motor function was assessed using a rotarod test. Additionally, immunofluorescence technology was used to analyze the DA neurons in the midbrain of PD rats, and immunohistochemistry and Western blot analysis were employed to evaluate the expression levels and effects of proNGF-p75NTR-sortilin in the midbrain following HF rTMS. Results Our research revealed a significant increase of proNGF expression in reactive astrocytes and upregulated sortilin and p75NTR in DA neurons in the substantia nigra of the hemisphere ipsilateral to the induced lesion, correlated with the degeneration of DA neurons and impaired motor functions. A four-week regimen of HF rTMS, as opposed to sham rTMS, significantly improved the above pathological conditions. The decrease in proNGF-p75NTR-sortilin expression following HF rTMS correlated with a significant increase in DA neuron survival and motor function improvement. HF rTMS exhibited no effects on proBDNF expression. Our study findings indicate that the targeted proNGF-p75NTR-sortilin complex modulation may be an essential mechanism through which HF rTMS exerts its neuroprotective effect. This insight offers a new therapeutic perspective for PD management, highlighting the potential of rTMS to modulate key neurodegenerative pathways. |
| format | Article |
| id | doaj-art-e4d63681ccda4b0695ec11f280ff91f8 |
| institution | Kabale University |
| issn | 2167-8359 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj-art-e4d63681ccda4b0695ec11f280ff91f82025-08-20T03:31:24ZengPeerJ Inc.PeerJ2167-83592025-07-0113e1963310.7717/peerj.19633High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathwayRui Zhao0Wanqing Du1Ke Tian2Kunlong Zhang3Hua Yuan4Fang Gao5Xin Kang6Xiaolong Sun7Department of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Neurobiology, Institute of Neurosciences, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaDepartment of Rehabilitation Medicine, Xijing Hospital, Fouth Military Medical University, Xi’an, ChinaBackground High-frequency repetitive transcranial magnetic stimulation (HF rTMS) is a promising non-invasive treatment for Parkinson’s disease (PD) in clinical settings. However, the precise mechanisms are incompletely understood. The proNGF-p75NTR-sortilin signaling pathway is closely associated with nigrostriatal dopaminergic (DA) neuron degeneration, a hallmark feature of PD. This study aimed to evaluate the neuroprotective efficacy of HF rTMS on the proNGF-p75NTR-sortilin pathway in PD. Methods Using a PD rat model induced by 6-hydroxydopamine (6-OHDA), the rats were randomly divided into two groups: sham rTMS group and HF rTMS group. After a 4 w intervention, the rats’ motor function was assessed using a rotarod test. Additionally, immunofluorescence technology was used to analyze the DA neurons in the midbrain of PD rats, and immunohistochemistry and Western blot analysis were employed to evaluate the expression levels and effects of proNGF-p75NTR-sortilin in the midbrain following HF rTMS. Results Our research revealed a significant increase of proNGF expression in reactive astrocytes and upregulated sortilin and p75NTR in DA neurons in the substantia nigra of the hemisphere ipsilateral to the induced lesion, correlated with the degeneration of DA neurons and impaired motor functions. A four-week regimen of HF rTMS, as opposed to sham rTMS, significantly improved the above pathological conditions. The decrease in proNGF-p75NTR-sortilin expression following HF rTMS correlated with a significant increase in DA neuron survival and motor function improvement. HF rTMS exhibited no effects on proBDNF expression. Our study findings indicate that the targeted proNGF-p75NTR-sortilin complex modulation may be an essential mechanism through which HF rTMS exerts its neuroprotective effect. This insight offers a new therapeutic perspective for PD management, highlighting the potential of rTMS to modulate key neurodegenerative pathways.https://peerj.com/articles/19633.pdfParkinson’s diseaseRepetitive transcranial magnetic stimulationSortilinproNGFDA neurons6-hydroxydopamine |
| spellingShingle | Rui Zhao Wanqing Du Ke Tian Kunlong Zhang Hua Yuan Fang Gao Xin Kang Xiaolong Sun High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway PeerJ Parkinson’s disease Repetitive transcranial magnetic stimulation Sortilin proNGF DA neurons 6-hydroxydopamine |
| title | High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway |
| title_full | High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway |
| title_fullStr | High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway |
| title_full_unstemmed | High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway |
| title_short | High-frequency repetitive transcranial magnetic stimulation protects against 6-OHDA-induced Parkinson’s disease symptoms by modulating the proNGF-p75NTR-sortilin pathway |
| title_sort | high frequency repetitive transcranial magnetic stimulation protects against 6 ohda induced parkinson s disease symptoms by modulating the prongf p75ntr sortilin pathway |
| topic | Parkinson’s disease Repetitive transcranial magnetic stimulation Sortilin proNGF DA neurons 6-hydroxydopamine |
| url | https://peerj.com/articles/19633.pdf |
| work_keys_str_mv | AT ruizhao highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT wanqingdu highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT ketian highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT kunlongzhang highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT huayuan highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT fanggao highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT xinkang highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway AT xiaolongsun highfrequencyrepetitivetranscranialmagneticstimulationprotectsagainst6ohdainducedparkinsonsdiseasesymptomsbymodulatingtheprongfp75ntrsortilinpathway |