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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Amyotrophic Lateral Sclerosis | Research

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

Authors: Javier H. Jara, Mukesh Gautam, Nuran Kocak, Edward F. Xie, Qinwen Mao, Eileen H. Bigio, P. Hande Özdinler

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

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-43A315T-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.
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Metadata
Title
MCP1-CCR2 and neuroinflammation in the ALS motor cortex with TDP-43 pathology
Authors
Javier H. Jara
Mukesh Gautam
Nuran Kocak
Edward F. Xie
Qinwen Mao
Eileen H. Bigio
P. Hande Özdinler
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1589-y

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