PMID- 27554772
OWN - NLM
STAT- MEDLINE
DCOM- 20170828
LR  - 20181202
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 74
IP  - 2
DP  - 2017 Jan
TI  - Disruption of calcitonin gene-related peptide signaling accelerates muscle 
      denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice.
PG  - 339-358
LID - 10.1007/s00018-016-2337-4 [doi]
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal 
      vacuolization and glial activation are pathologic hallmarks in the superoxide 
      dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide 
      calcitonin gene-related peptide (CGRP) associated with vacuolization and 
      astrogliosis in the spinal cord of these mice. We now show that CGRP abundance 
      positively correlated with the severity of astrogliosis, but not vacuolization, 
      in several motor and non-motor areas throughout the brain. SOD1 mice harboring a 
      genetic depletion of the betaCGRP isoform showed reduced CGRP immunoreactivity 
      associated with vacuolization, while motor functions, body weight, survival, and 
      astrogliosis were not altered. When CGRP signaling was completely disrupted 
      through genetic depletion of the CGRP receptor component, receptor 
      activity-modifying protein 1 (RAMP1), hind limb muscle denervation, and loss of 
      muscle performance were accelerated, while body weight and survival were not 
      affected. Dampened neuroinflammation, i.e., reduced levels of astrogliosis in the 
      brain stem already in the pre-symptomatic disease stage, and reduced microgliosis 
      and lymphocyte infiltrations during the late disease phase were additional 
      neuropathology features in these mice. On the molecular level, mRNA expression 
      levels of brain-derived neurotrophic factor (BDNF) and those of the 
      anti-inflammatory cytokine interleukin 6 (IL-6) were elevated, while those of 
      several pro-inflammatory cytokines found reduced in the brain stem of 
      RAMP1-deficient SOD1 mice at disease end stage. Our results thus identify an 
      important, possibly dual role of CGRP in ALS pathogenesis.
FAU - Ringer, Cornelia
AU  - Ringer C
AD  - Department of Molecular Neurosciences, Institute of Anatomy and Cell Biology, 
      Philipps-University, Robert-Koch-Strasse 8, 35037, Marburg, Germany.
AD  - Institute of Anatomy, University of Lubeck, Lubeck, Germany.
FAU - Tune, Sarah
AU  - Tune S
AD  - Department of Physiology, University of Lubeck, Lubeck, Germany.
FAU - Bertoune, Mirjam A
AU  - Bertoune MA
AD  - Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, 
      Philipps-University, Marburg, Germany.
FAU - Schwarzbach, Hans
AU  - Schwarzbach H
AD  - Department of Medical Cell Biology, Institute of Anatomy and Cell Biology, 
      Philipps-University, Marburg, Germany.
FAU - Tsujikawa, Kazutake
AU  - Tsujikawa K
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
FAU - Weihe, Eberhard
AU  - Weihe E
AD  - Department of Molecular Neurosciences, Institute of Anatomy and Cell Biology, 
      Philipps-University, Robert-Koch-Strasse 8, 35037, Marburg, Germany. 
      weihe@staff.uni-marburg.de.
FAU - Schutz, Burkhard
AU  - Schutz B
AD  - Department of Molecular Neurosciences, Institute of Anatomy and Cell Biology, 
      Philipps-University, Robert-Koch-Strasse 8, 35037, Marburg, Germany. 
      schuetzb@staff.uni-marburg.de.
LA  - eng
PT  - Journal Article
DEP - 20160823
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Chemokines)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Ramp1 protein, mouse)
RN  - 0 (Receptor Activity-Modifying Protein 1)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - Brain/metabolism/*pathology
MH  - Calcitonin Gene-Related Peptide/*metabolism
MH  - Cell Death
MH  - Chemokines/metabolism
MH  - Disease Progression
MH  - Gene Expression Regulation
MH  - Humans
MH  - Hybridization, Genetic
MH  - Inflammation/*metabolism/*pathology
MH  - Lymphocytes/pathology
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Models, Biological
MH  - Motor Neurons/metabolism/pathology
MH  - *Muscle Denervation
MH  - Nerve Growth Factors/metabolism
MH  - Receptor Activity-Modifying Protein 1/deficiency/metabolism
MH  - *Signal Transduction
MH  - Superoxide Dismutase-1/*genetics/metabolism
MH  - Vacuoles/metabolism
OTO - NOTNLM
OT  - Astrocyte
OT  - Chemokine
OT  - Microglia
OT  - Neuropeptide
OT  - Receptor activity-modifying protein 1
OT  - Superoxide dismutase 1
EDAT- 2016/08/25 06:00
MHDA- 2017/08/29 06:00
CRDT- 2016/08/25 06:00
PHST- 2016/01/28 00:00 [received]
PHST- 2016/08/08 00:00 [accepted]
PHST- 2016/08/06 00:00 [revised]
PHST- 2016/08/25 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2016/08/25 06:00 [entrez]
AID - 10.1007/s00018-016-2337-4 [pii]
AID - 10.1007/s00018-016-2337-4 [doi]
PST - ppublish
SO  - Cell Mol Life Sci. 2017 Jan;74(2):339-358. doi: 10.1007/s00018-016-2337-4. Epub 
      2016 Aug 23.