TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF.

Abstract

Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.

• Authors: Jin H Nam, Eun S Park, So-Yoon Won, Yu A Lee, Kyoung I Kim, Jae Y Jeong, Jeong Y Baek, Eun J Cho, Minyoung Jin, Young C Chung, Byoung D Lee, Sung Hyun Kim, Eung-Gook Kim, Kyunghee Byun, Bonghee Lee, Dong Ho Woo, C Justin Lee, Sang R Kim, Eugene Bok, Yoon-Seong Kim, Tae-Beom Ahn, Hyuk Wan Ko, Saurav Brahmachari, Olga Pletinkova, Juan C Troconso, Valina L Dawson, Ted M Dawson, Byung K Jin
• Journal: Brain : a journal of neurology (Brain) Vol. 138 Issue Pt 12 Pg. 3610-22 (Dec 2015) ISSN: 1460-2156 [Electronic] England
• PMID: 26490328 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• Ciliary Neurotrophic Factor
• Ciliary Neurotrophic Factor Receptor alpha Subunit
• TRPV Cation Channels
• TRPV1 receptor

Topics

• Animals
• Astrocytes (metabolism)
• Ciliary Neurotrophic Factor (metabolism)
• Ciliary Neurotrophic Factor Receptor alpha Subunit (metabolism)
• Disease Models, Animal
• Dopaminergic Neurons (metabolism, pathology)
• Female
• Humans
• Nerve Regeneration
• Neuroprotection
• Parkinson Disease (metabolism, pathology, physiopathology)
• Rats
• Substantia Nigra (cytology, metabolism, pathology)
• TRPV Cation Channels (metabolism)