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

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, Changjoon Lee, Sang R. Kim, Eugene Bok, Yoon Seong KimTae Beom Ahn, Hyuk Wan Ko, Saurav Brahmachari, Olga Pletinkova, Juan C. Troconso, Valina L. Dawson, Ted M. Dawson, Byung K. Jin

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3610-3622
Number of pages13
JournalBrain
Volume138
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1
Externally publishedYes

Fingerprint

Ciliary Neurotrophic Factor
Dopaminergic Neurons
Substantia Nigra
Astrocytes
Parkinson Disease
Ciliary Neurotrophic Factor Receptor
Synucleins
Dependovirus
Western Blotting
vanilloid receptor subtype 1
Neuron
Rescue
Parkinson's Disease
Dopamine
Therapeutics

Keywords

  • astrocyte
  • ciliary neurotrophic factor (CNTF)
  • dopamine neurons
  • Parkinson's disease
  • TRPV1

ASJC Scopus subject areas

  • Medicine(all)
  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Nam, J. H., Park, E. S., Won, S. Y., Lee, Y. A., Kim, K. I., Jeong, J. Y., ... Jin, B. K. (2015). TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF. Brain, 138(12), 3610-3622. https://doi.org/10.1093/brain/awv297

TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF. / Nam, Jin H.; Park, Eun S.; Won, So Yoon; Lee, Yu A.; Kim, Kyoung I.; Jeong, Jae Y.; Baek, Jeong Y.; Cho, Eun J.; Jin, Minyoung; Chung, Young C.; Lee, Byoung D.; Kim, Sung Hyun; Kim, Eung Gook; Byun, Kyunghee; Lee, Bonghee; Woo, Dong Ho; Lee, Changjoon; Kim, Sang R.; Bok, Eugene; Kim, Yoon Seong; Ahn, Tae Beom; Ko, Hyuk Wan; Brahmachari, Saurav; Pletinkova, Olga; Troconso, Juan C.; Dawson, Valina L.; Dawson, Ted M.; Jin, Byung K.

In: Brain, Vol. 138, No. 12, 01.12.2015, p. 3610-3622.

Research output: Contribution to journalArticle

Nam, JH, Park, ES, Won, SY, Lee, YA, Kim, KI, Jeong, JY, Baek, JY, Cho, EJ, Jin, M, Chung, YC, Lee, BD, Kim, SH, Kim, EG, Byun, K, Lee, B, Woo, DH, Lee, C, Kim, SR, Bok, E, Kim, YS, Ahn, TB, Ko, HW, Brahmachari, S, Pletinkova, O, Troconso, JC, Dawson, VL, Dawson, TM & Jin, BK 2015, 'TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF', Brain, vol. 138, no. 12, pp. 3610-3622. https://doi.org/10.1093/brain/awv297
Nam JH, Park ES, Won SY, Lee YA, Kim KI, Jeong JY et al. TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF. Brain. 2015 Dec 1;138(12):3610-3622. https://doi.org/10.1093/brain/awv297
Nam, Jin H. ; Park, Eun S. ; Won, So Yoon ; Lee, Yu A. ; Kim, Kyoung I. ; Jeong, Jae Y. ; Baek, Jeong Y. ; Cho, Eun J. ; Jin, Minyoung ; Chung, Young C. ; Lee, Byoung D. ; Kim, Sung Hyun ; Kim, Eung Gook ; Byun, Kyunghee ; Lee, Bonghee ; Woo, Dong Ho ; Lee, Changjoon ; Kim, Sang R. ; Bok, Eugene ; Kim, Yoon Seong ; Ahn, Tae Beom ; Ko, Hyuk Wan ; Brahmachari, Saurav ; Pletinkova, Olga ; Troconso, Juan C. ; Dawson, Valina L. ; Dawson, Ted M. ; Jin, Byung K. / TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF. In: Brain. 2015 ; Vol. 138, No. 12. pp. 3610-3622.
@article{cb8b06c2c2534709b645f60aa212efca,
title = "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.",
keywords = "astrocyte, ciliary neurotrophic factor (CNTF), dopamine neurons, Parkinson's disease, TRPV1",
author = "Nam, {Jin H.} and Park, {Eun S.} and Won, {So Yoon} and Lee, {Yu A.} and Kim, {Kyoung I.} and Jeong, {Jae Y.} and Baek, {Jeong Y.} and Cho, {Eun J.} and Minyoung Jin and Chung, {Young C.} and Lee, {Byoung D.} and Kim, {Sung Hyun} and Kim, {Eung Gook} and Kyunghee Byun and Bonghee Lee and Woo, {Dong Ho} and Changjoon Lee and Kim, {Sang R.} and Eugene Bok and Kim, {Yoon Seong} and Ahn, {Tae Beom} and Ko, {Hyuk Wan} and Saurav Brahmachari and Olga Pletinkova and Troconso, {Juan C.} and Dawson, {Valina L.} and Dawson, {Ted M.} and Jin, {Byung K.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1093/brain/awv297",
language = "English",
volume = "138",
pages = "3610--3622",
journal = "Brain : a journal of neurology",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - TRPV1 on astrocytes rescues nigral dopamine neurons in Parkinson's disease via CNTF

AU - Nam, Jin H.

AU - Park, Eun S.

AU - Won, So Yoon

AU - Lee, Yu A.

AU - Kim, Kyoung I.

AU - Jeong, Jae Y.

AU - Baek, Jeong Y.

AU - Cho, Eun J.

AU - Jin, Minyoung

AU - Chung, Young C.

AU - Lee, Byoung D.

AU - Kim, Sung Hyun

AU - Kim, Eung Gook

AU - Byun, Kyunghee

AU - Lee, Bonghee

AU - Woo, Dong Ho

AU - Lee, Changjoon

AU - Kim, Sang R.

AU - Bok, Eugene

AU - Kim, Yoon Seong

AU - Ahn, Tae Beom

AU - Ko, Hyuk Wan

AU - Brahmachari, Saurav

AU - Pletinkova, Olga

AU - Troconso, Juan C.

AU - Dawson, Valina L.

AU - Dawson, Ted M.

AU - Jin, Byung K.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - 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.

AB - 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.

KW - astrocyte

KW - ciliary neurotrophic factor (CNTF)

KW - dopamine neurons

KW - Parkinson's disease

KW - TRPV1

UR - http://www.scopus.com/inward/record.url?scp=84951197871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84951197871&partnerID=8YFLogxK

U2 - 10.1093/brain/awv297

DO - 10.1093/brain/awv297

M3 - Article

C2 - 26490328

AN - SCOPUS:84951197871

VL - 138

SP - 3610

EP - 3622

JO - Brain : a journal of neurology

JF - Brain : a journal of neurology

SN - 0006-8950

IS - 12

ER -