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Hepatocyte growth factor (HGF) attenuates gliosis and motoneuronal degeneration in the brainstem motor nuclei of a transgenic mouse model of ALS
- Source :
- Neuroscience Research. 59:446-456
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- 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 SOD1G93A 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.
- Subjects :
- Male
Genetically modified mouse
C-Met
Mice, Transgenic
Biology
Mice
chemistry.chemical_compound
Superoxide Dismutase-1
medicine
Animals
Humans
Gliosis
Chemokine CCL2
Motor Neurons
Microglia
Hepatocyte Growth Factor
Superoxide Dismutase
General Neuroscience
Amyotrophic Lateral Sclerosis
Cranial Nerves
General Medicine
XIAP
Mice, Inbred C57BL
Disease Models, Animal
Neuroprotective Agents
Treatment Outcome
medicine.anatomical_structure
nervous system
chemistry
Astrocytes
Nerve Degeneration
Immunology
Cancer research
biology.protein
Female
Hepatocyte growth factor
Brainstem
medicine.symptom
Apoptosis Regulatory Proteins
Brain Stem
medicine.drug
Neurotrophin
Subjects
Details
- ISSN :
- 01680102
- Volume :
- 59
- Database :
- OpenAIRE
- Journal :
- Neuroscience Research
- Accession number :
- edsair.doi.dedup.....9b2966b3a651a0ed353e42aa15021cb6