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RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease

Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated...

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Autores principales: Qiao, Chenmeng, Niu, Guyu, Zhao, Weijiang, Quan, Wei, Zhou, Yu, Zhang, Meixuan, Li, Ting, Zhou, Shengyang, Huang, Wenyan, Zhao, Liping, Wu, Jian, Cui, Chun, Shen, Yanqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216483/
https://www.ncbi.nlm.nih.gov/pubmed/37239205
http://dx.doi.org/10.3390/brainsci13050733
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author Qiao, Chenmeng
Niu, Guyu
Zhao, Weijiang
Quan, Wei
Zhou, Yu
Zhang, Meixuan
Li, Ting
Zhou, Shengyang
Huang, Wenyan
Zhao, Liping
Wu, Jian
Cui, Chun
Shen, Yanqin
author_facet Qiao, Chenmeng
Niu, Guyu
Zhao, Weijiang
Quan, Wei
Zhou, Yu
Zhang, Meixuan
Li, Ting
Zhou, Shengyang
Huang, Wenyan
Zhao, Liping
Wu, Jian
Cui, Chun
Shen, Yanqin
author_sort Qiao, Chenmeng
collection PubMed
description Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated in the brain in PD mouse models. Here, we aim to explore the role of RIPK1 in regulating the neuroinflammation of PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg four times/day), followed by necrostatin-1 treatment (Nec-1, RIPK1 inhibitor; 1.65 mg/kg once daily for seven days. Notably, the first Nec-1 was given 12 h before MPTP modeling). Behavioral tests indicated that inhibition of RIPK1 greatly relieved motor dysfunction and anxiety-like behaviors of PD mice. It also increased striatal TH expression, rescue the loss of dopaminergic neurons, and reduce activation of astrocytes in the striatum of PD mice. Furthermore, inhibition of RIPK1 expression reduced A1 astrocytes’ relative gene expression (CFB, H2-T23) and inflammatory cytokine or chemokine production (CCL2, TNF-α, IL-1β) in the striatum of PD mice. Collectively, inhibition of RIPK1 expression can provide neuroprotection to PD mice, probably through inhibition of the astrocyte A1 phenotype, and thus RIPK1 might be an important target in PD treatment.
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spelling pubmed-102164832023-05-27 RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease Qiao, Chenmeng Niu, Guyu Zhao, Weijiang Quan, Wei Zhou, Yu Zhang, Meixuan Li, Ting Zhou, Shengyang Huang, Wenyan Zhao, Liping Wu, Jian Cui, Chun Shen, Yanqin Brain Sci Article Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated in the brain in PD mouse models. Here, we aim to explore the role of RIPK1 in regulating the neuroinflammation of PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg four times/day), followed by necrostatin-1 treatment (Nec-1, RIPK1 inhibitor; 1.65 mg/kg once daily for seven days. Notably, the first Nec-1 was given 12 h before MPTP modeling). Behavioral tests indicated that inhibition of RIPK1 greatly relieved motor dysfunction and anxiety-like behaviors of PD mice. It also increased striatal TH expression, rescue the loss of dopaminergic neurons, and reduce activation of astrocytes in the striatum of PD mice. Furthermore, inhibition of RIPK1 expression reduced A1 astrocytes’ relative gene expression (CFB, H2-T23) and inflammatory cytokine or chemokine production (CCL2, TNF-α, IL-1β) in the striatum of PD mice. Collectively, inhibition of RIPK1 expression can provide neuroprotection to PD mice, probably through inhibition of the astrocyte A1 phenotype, and thus RIPK1 might be an important target in PD treatment. MDPI 2023-04-27 /pmc/articles/PMC10216483/ /pubmed/37239205 http://dx.doi.org/10.3390/brainsci13050733 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Qiao, Chenmeng
Niu, Guyu
Zhao, Weijiang
Quan, Wei
Zhou, Yu
Zhang, Meixuan
Li, Ting
Zhou, Shengyang
Huang, Wenyan
Zhao, Liping
Wu, Jian
Cui, Chun
Shen, Yanqin
RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title_full RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title_fullStr RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title_full_unstemmed RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title_short RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
title_sort ripk1-induced a1 reactive astrocytes in brain in mptp-treated murine model of parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216483/
https://www.ncbi.nlm.nih.gov/pubmed/37239205
http://dx.doi.org/10.3390/brainsci13050733
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