MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology.

Autor: Jara JH; Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA.; Les Turner ALS Center, Chicago, USA., Gautam M; Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA.; Les Turner ALS Center, Chicago, USA., Kocak N; Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA.; Les Turner ALS Center, Chicago, USA., Xie EF; Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA.; Les Turner ALS Center, Chicago, USA., Mao Q; Department of Pathology, Northwestern University, Chicago, USA.; Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, USA., Bigio EH; Department of Pathology, Northwestern University, Chicago, USA.; Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, USA., Özdinler PH; Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA. ozdinler@northwestern.edu.; Les Turner ALS Center, Chicago, USA. ozdinler@northwestern.edu.; Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University Feinberg School of Medicine, Chicago, USA. ozdinler@northwestern.edu.; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA. ozdinler@northwestern.edu.; Department of Neurology, 303 E Chicago Ave., Ward 10-015, Chicago, IL, 60611, USA. ozdinler@northwestern.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2019 Oct 30; Vol. 16 (1), pp. 196. Date of Electronic Publication: 2019 Oct 30.
DOI: 10.1186/s12974-019-1589-y
Abstrakt: 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: We investigated the presence of astrogliosis and microgliosis in the motor cortex of ALS patients with TDP-43 pathology. prpTDP-43 A315T -UeGFP mice, corticospinal motor neuron (CSMN) reporter line with TDP-43 pathology, are utilized to reveal the timing and extent of neuroimmune interactions and the involvement of non-neuronal cells to neurodegeneration. Electron microscopy and immunolabeling techniques are used to mark and monitor cells of interest.
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: 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.
Databáze: MEDLINE
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