PMID- 28651542
OWN - NLM
STAT- MEDLINE
DCOM- 20180411
LR  - 20181113
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 14
IP  - 1
DP  - 2017 Jun 26
TI  - Evidence for an early innate immune response in the motor cortex of ALS.
PG  - 129
LID - 10.1186/s12974-017-0896-4 [doi]
LID - 129
AB  - 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-hSOD1(G93A) 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-hSOD1(G93A) 
      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.
FAU - Jara, Javier H
AU  - Jara JH
AD  - Department of Neurology and Clinical Neurological Sciences, Northwestern 
      University Feinberg School of Medicine, 303 E. Chicago Ave. Ward 10-120, Chicago, 
      IL, 60611, USA. j-jara@northwestern.edu.
FAU - Genc, Baris
AU  - Genc B
AD  - Department of Neurology and Clinical Neurological Sciences, Northwestern 
      University Feinberg School of Medicine, 303 E. Chicago Ave. Ward 10-120, Chicago, 
      IL, 60611, USA.
FAU - Stanford, Macdonell J
AU  - Stanford MJ
AD  - Department of Neurology and Clinical Neurological Sciences, Northwestern 
      University Feinberg School of Medicine, 303 E. Chicago Ave. Ward 10-120, Chicago, 
      IL, 60611, USA.
FAU - Pytel, Peter
AU  - Pytel P
AD  - Department of Pathology, University of Chicago Medical Center, Chicago, IL, 
      60637, USA.
FAU - Roos, Raymond P
AU  - Roos RP
AD  - Department of Neurology, University of Chicago Medical Center, Chicago, IL, 
      60637, USA.
FAU - Weintraub, Sandra
AU  - Weintraub S
AD  - Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, 
      Chicago, IL, 60611, USA.
FAU - Mesulam, M Marsel
AU  - Mesulam MM
AD  - Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, 
      Chicago, IL, 60611, USA.
FAU - Bigio, Eileen H
AU  - Bigio EH
AD  - Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, 
      Chicago, IL, 60611, USA.
FAU - Miller, Richard J
AU  - Miller RJ
AD  - Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg 
      School of Medicine, Chicago, IL, 60611, USA.
FAU - Ozdinler, P Hande
AU  - Ozdinler PH
AUID- ORCID: 0000-0003-4125-6013
AD  - Department of Neurology and Clinical Neurological Sciences, Northwestern 
      University Feinberg School of Medicine, 303 E. Chicago Ave. Ward 10-120, Chicago, 
      IL, 60611, USA. ozdinler@northwestern.edu.
AD  - Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, 
      Chicago, IL, 60611, USA. ozdinler@northwestern.edu.
AD  - Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, 60611, USA. 
      ozdinler@northwestern.edu.
LA  - eng
GR  - P30 AG013854/AG/NIA NIH HHS/United States
GR  - UL1 TR001422/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170626
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Amyotrophic Lateral Sclerosis/genetics/*immunology/*pathology
MH  - Animals
MH  - Female
MH  - Humans
MH  - Immunity, Innate/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microglia/immunology/pathology
MH  - Middle Aged
MH  - Motor Cortex/*immunology/*pathology
PMC - PMC5485686
OTO - NOTNLM
OT  - CCR2
OT  - MCP1
OT  - Microglia
OT  - Upper motor neurons
EDAT- 2017/06/28 06:00
MHDA- 2018/04/12 06:00
PMCR- 2017/06/26
CRDT- 2017/06/28 06:00
PHST- 2017/01/13 00:00 [received]
PHST- 2017/06/12 00:00 [accepted]
PHST- 2017/06/28 06:00 [entrez]
PHST- 2017/06/28 06:00 [pubmed]
PHST- 2018/04/12 06:00 [medline]
PHST- 2017/06/26 00:00 [pmc-release]
AID - 10.1186/s12974-017-0896-4 [pii]
AID - 896 [pii]
AID - 10.1186/s12974-017-0896-4 [doi]
PST - epublish
SO  - J Neuroinflammation. 2017 Jun 26;14(1):129. doi: 10.1186/s12974-017-0896-4.