Evidence for an early innate immune response in the motor cortex of ALS
| Autor: | Peter Pytel, Sandra Weintraub, Barış Genç, Raymond P. Roos, Richard J. Miller, Javier H. Jara, P. Hande Özdinler, Eileen H. Bigio, M.-Marsel Mesulam, Macdonell J. Stanford |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male CCR2 Immunology Mice Transgenic Upper motor neurons Biology lcsh:RC346-429 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine medicine Animals Humans Amyotrophic lateral sclerosis Neuroinflammation lcsh:Neurology. Diseases of the nervous system Aged Aged 80 and over Innate immune system Microglia Upper motor neuron General Neuroscience Research Amyotrophic Lateral Sclerosis Motor Cortex Motor neuron Middle Aged medicine.disease Immunity Innate Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neurology MCP1 Female Neuroscience 030217 neurology & neurosurgery Motor cortex |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-20 (2017) |
| ISSN: | 1742-2094 |
| Popis: | Background Recent evidence indicates the importance of innate immunity and neuroinflammation with microgliosis in amyotrophic lateral sclerosis (ALS) pathology. The MCP1 (monocyte chemoattractant protein-1) and CCR2 (CC chemokine receptor 2) signaling system has been strongly associated with the innate immune responses observed in ALS patients, but the motor cortex has not been studied in detail. Methods After revealing the presence of MCP1 and CCR2 in the motor cortex of ALS patients, to elucidate, visualize, and define the timing, location and the extent of immune response in relation to upper motor neuron vulnerability and progressive degeneration in ALS, we developed MCP1-CCR2-hSOD1G93A mice, an ALS reporter line, in which cells expressing MCP1 and CCR2 are genetically labeled by monomeric red fluorescent protein-1 and enhanced green fluorescent protein, respectively. Results In the motor cortex of MCP1-CCR2-hSOD1G93A mice, unlike in the spinal cord, there was an early increase in the numbers of MCP1+ cells, which displayed microglial morphology and selectively expressed microglia markers. Even though fewer CCR2+ cells were present throughout the motor cortex, they were mainly infiltrating monocytes. Interestingly, MCP1+ cells were found in close proximity to the apical dendrites and cell bodies of corticospinal motor neurons (CSMN), further implicating the importance of their cellular interaction to neuronal pathology. Similar findings were observed in the motor cortex of ALS patients, where MCP1+ microglia were especially in close proximity to the degenerating apical dendrites of Betz cells. Conclusions Our findings reveal that the intricate cellular interplay between immune cells and upper motor neurons observed in the motor cortex of ALS mice is indeed recapitulated in ALS patients. We generated and characterized a novel model system, to study the cellular and molecular basis of this close cellular interaction and how that relates to motor neuron vulnerability and progressive degeneration in ALS. Electronic supplementary material The online version of this article (doi:10.1186/s12974-017-0896-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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