MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology.
MCP1-CCR2 axis
Microglia
TDP-43
Upper motor neurons
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
30 Oct 2019
30 Oct 2019
Historique:
received:
07
05
2019
accepted:
13
09
2019
entrez:
1
11
2019
pubmed:
2
11
2019
medline:
31
3
2020
Statut:
epublish
Résumé
The involvement of non-neuronal cells and the cells of innate immunity has been attributed to the initiation and progression of ALS. TDP-43 pathology is observed in a broad spectrum of ALS cases and is one of the most commonly shared pathologies. The potential involvement of the neuroimmune axis in the motor cortex of ALS patients with TDP-43 pathology needs to be revealed. This information is vital for building effective treatment strategies. We investigated the presence of astrogliosis and microgliosis in the motor cortex of ALS patients with TDP-43 pathology. prpTDP-43 We detected both activated astrocytes and microglia, especially rod-like microglia, in the motor cortex of patients and TDP-43 mouse model. Besides, CCR2+ TMEM119- infiltrating monocytes were detected as they penetrate the brain parenchyma. Interestingly, Betz cells, which normally do not express MCP1, were marked with high levels of MCP1 expression when diseased. There is an early contribution of a neuroinflammatory response for upper motor neuron (UMN) degeneration with respect to TDP-43 pathology, and MCP1-CCR2 signaling is important for the recognition of diseased upper motor neurons by infiltrating monocytes. The findings are conserved among species and are observed in both ALS and ALS-FTLD patients.
Sections du résumé
BACKGROUND
BACKGROUND
The involvement of non-neuronal cells and the cells of innate immunity has been attributed to the initiation and progression of ALS. TDP-43 pathology is observed in a broad spectrum of ALS cases and is one of the most commonly shared pathologies. The potential involvement of the neuroimmune axis in the motor cortex of ALS patients with TDP-43 pathology needs to be revealed. This information is vital for building effective treatment strategies.
METHODS
METHODS
We investigated the presence of astrogliosis and microgliosis in the motor cortex of ALS patients with TDP-43 pathology. prpTDP-43
RESULTS
RESULTS
We detected both activated astrocytes and microglia, especially rod-like microglia, in the motor cortex of patients and TDP-43 mouse model. Besides, CCR2+ TMEM119- infiltrating monocytes were detected as they penetrate the brain parenchyma. Interestingly, Betz cells, which normally do not express MCP1, were marked with high levels of MCP1 expression when diseased.
CONCLUSIONS
CONCLUSIONS
There is an early contribution of a neuroinflammatory response for upper motor neuron (UMN) degeneration with respect to TDP-43 pathology, and MCP1-CCR2 signaling is important for the recognition of diseased upper motor neurons by infiltrating monocytes. The findings are conserved among species and are observed in both ALS and ALS-FTLD patients.
Identifiants
pubmed: 31666087
doi: 10.1186/s12974-019-1589-y
pii: 10.1186/s12974-019-1589-y
pmc: PMC6822373
doi:
Substances chimiques
CCR2 protein, human
0
DNA-Binding Proteins
0
Receptors, CCR2
0
TARDBP protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
196Subventions
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS085750
Pays : United States
Organisme : ALS Association
ID : Milton Safenowitz Postdoctoral Fellowship
Organisme : NIH HHS
ID : R21-NS085750
Pays : United States
Organisme : NIH/NIA
ID : AG13854
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