PMID- 17935811
OWN - NLM
STAT- MEDLINE
DCOM- 20080111
LR  - 20210924
IS  - 0168-0102 (Print)
IS  - 0168-0102 (Linking)
VI  - 59
IP  - 4
DP  - 2007 Dec
TI  - Hepatocyte growth factor (HGF) attenuates gliosis and motoneuronal degeneration 
      in the brainstem motor nuclei of a transgenic mouse model of ALS.
PG  - 446-56
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease 
      characterized by progressive loss of brainstem and spinal motoneurons. Although 
      prevention of motoneuronal degeneration has been postulated as the primary target 
      for a cure, accumulating evidence suggests that microglial accumulation 
      contributes to disease progression. This study was designed to assess the ability 
      of HGF to modulate microglial accumulation and motoneuronal degeneration in 
      brainstem motor nuclei, using double transgenic mice overexpressing mutated 
      SOD1(G93A) and HGF (G93A/HGF). Histological and immunohistochemical analyses of 
      the tissues of G93A/HGF mice revealed a marked decrease in the number of 
      microglia and reactive astrocytes and an attenuation of the loss of motoneurons 
      in facial and hypoglossal nuclei compared with G93A mice. HGF overexpression 
      attenuated monocyte chemoattractant protein-1 (MCP-1) induction, predominantly in 
      astrocytes; suppressed activation of caspase-1, -3 and -9; and, increased X 
      chromosome-linked inhibition of apoptosis protein (XIAP) in the motoneurons of 
      G93A mice. The implication is that HGF reduces microglial accumulation by 
      suppressing MCP-1 induction and prevents motoneuronal death through inhibition of 
      pro-apoptotic protein activation. These findings suggest that, in addition to 
      direct neurotrophic activity on motoneurons, HGF-suppression of gliosis may 
      retard disease progression, making HGF a potential therapeutic agent for the 
      treatment of ALS patients.
FAU - Kadoyama, Keiichi
AU  - Kadoyama K
AD  - Division of Molecular Regenerative Medicine, Department of Biochemistry and 
      Molecular Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
FAU - Funakoshi, Hiroshi
AU  - Funakoshi H
FAU - Ohya, Wakana
AU  - Ohya W
FAU - Nakamura, Toshikazu
AU  - Nakamura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070831
PL  - Ireland
TA  - Neurosci Res
JT  - Neuroscience research
JID - 8500749
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (SOD1 protein, human)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/*drug therapy/metabolism/physiopathology
MH  - Animals
MH  - Apoptosis Regulatory Proteins/drug effects/metabolism
MH  - Astrocytes/drug effects/metabolism/pathology
MH  - Brain Stem/*drug effects/metabolism/physiopathology
MH  - Chemokine CCL2/drug effects/metabolism
MH  - Cranial Nerves/drug effects/metabolism/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Gliosis/*drug therapy/physiopathology/prevention & control
MH  - Hepatocyte Growth Factor/*pharmacology/therapeutic use
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microglia/drug effects/metabolism/pathology
MH  - Motor Neurons/*drug effects/metabolism/pathology
MH  - Nerve Degeneration/drug therapy/physiopathology/prevention & control
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Superoxide Dismutase/genetics
MH  - Superoxide Dismutase-1
MH  - Treatment Outcome
EDAT- 2007/10/16 09:00
MHDA- 2008/01/12 09:00
CRDT- 2007/10/16 09:00
PHST- 2007/07/20 00:00 [received]
PHST- 2007/08/17 00:00 [revised]
PHST- 2007/08/20 00:00 [accepted]
PHST- 2007/10/16 09:00 [pubmed]
PHST- 2008/01/12 09:00 [medline]
PHST- 2007/10/16 09:00 [entrez]
AID - S0168-0102(07)01764-6 [pii]
AID - 10.1016/j.neures.2007.08.017 [doi]
PST - ppublish
SO  - Neurosci Res. 2007 Dec;59(4):446-56. doi: 10.1016/j.neures.2007.08.017. Epub 2007 
      Aug 31.