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Neuroprotective Activity of Peripherally Administered Liver Growth Factor in a Rat Model of Parkinson’s Disease
- Source :
- PLoS ONE, Vol 8, Iss 7, p e67771 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Liver growth factor (LGF) is a hepatic mitogen purified some years ago that promotes proliferation of different cell types and the regeneration of damaged tissues, including brain tissue. Considering the possibility that LGF could be used as a therapeutic agent in Parkinson’s disease, we analyzed its potential neuroregenerative and/or neuroprotective activity when peripherally administered to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats subjected to nigrostriatal lesions were treated intraperitoneally twice a week with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the last LGF treatment. The results show that LGF stimulates sprouting of tyrosine hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine transporter expression, as well as dopamine levels in the denervated striatum of 6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor necrosis factor-alpha protein levels, which have been reported to have a role in neuroregeneration and neuroprotection. Besides, LGF stimulates the phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins which are critical for cell survival such as Bcl2 and Akt. Because LGF partially protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and reduces motor deficits in these animals, we propose LGF as a novel factor that may be useful in the treatment of Parkinson’s disease.
- Subjects :
- Dopamine
lcsh:Medicine
Biochemistry
chemistry.chemical_compound
Molecular Cell Biology
Neurobiology of Disease and Regeneration
Cyclic AMP Response Element-Binding Protein
lcsh:Science
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Multidisciplinary
Behavior, Animal
biology
Neurochemistry
Parkinson Disease
Animal Models
Substantia Nigra
Neuroprotective Agents
Neurology
Medicine
Female
bcl-Associated Death Protein
Neurochemicals
Oxidopamine
Signal Transduction
Research Article
medicine.drug
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Serum Albumin, Human
Substantia nigra
Neuroprotection
Model Organisms
Internal medicine
medicine
Animals
Parkinson Disease, Secondary
Biology
Serum Albumin
Dopamine transporter
Dopamine Plasma Membrane Transport Proteins
Tyrosine hydroxylase
Tumor Necrosis Factor-alpha
lcsh:R
Neurotoxicity
Bilirubin
medicine.disease
Neuroregeneration
Corpus Striatum
Rats
Disease Models, Animal
Endocrinology
Gene Expression Regulation
chemistry
Cellular Neuroscience
biology.protein
Rat
lcsh:Q
Proto-Oncogene Proteins c-akt
Neuroscience
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c1c4abcdde6a2fc8425c0b66d2748c67