1-methyl-4-phenylpyridinium neurotoxicity is attenuated by adenoviral gene transfer of human Cu/Zn superoxide dismutase

Autor: Philippe Horellou, Jacques Mallet, Martine Barkats, Stéphanie Millecamps, Philippe Colin, Nicole Faucon-Biguet
Přispěvatelé: Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2006
Předmět:
1-Methyl-4-phenylpyridinium
MESH: Neurotoxicity Syndromes
Tetrazolium Salts
Cell Count
Striatum
MESH: Rotarod Performance Test
Pharmacology
Neuroblastoma
0302 clinical medicine
MESH: Genetic Vectors
MESH: Animals
Transgenes
MESH: Tyrosine 3-Monooxygenase
MESH: Superoxide Dismutase
MESH: 1-Methyl-4-phenylpyridinium
0303 health sciences
biology
Chemistry
Dopaminergic
Gene Transfer Techniques
Parkinson Disease
MESH: Tetrazolium Salts
Immunohistochemistry
MESH: Motor Activity
Substantia Nigra
Female
Neurotoxicity Syndromes
MESH: Cell Line
Tumor
Tyrosine 3-Monooxygenase
MESH: Rats
Genetic Vectors
SOD1
MESH: Substantia Nigra
MESH: Thiazoles
MESH: Transgenes
MESH: Gene Transfer Techniques
Substantia nigra
Motor Activity
Neuroprotection
Superoxide dismutase
03 medical and health sciences
Cellular and Molecular Neuroscience
Cell Line
Tumor
Dopaminergic Cell
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
MESH: Humans
Superoxide Dismutase
MESH: Cell Count
Neurotoxicity
MESH: Immunohistochemistry
Genetic Therapy
medicine.disease
MESH: Neuroblastoma
Molecular biology
Rats
Disease Models
Animal
Thiazoles
nervous system
Rotarod Performance Test
biology.protein
MESH: Disease Models
Animal
MESH: Gene Therapy
MESH: Female
MESH: Parkinson Disease
030217 neurology & neurosurgery
Zdroj: Journal of Neuroscience Research
Journal of Neuroscience Research, 2006, 83 (2), pp.233-42. ⟨10.1002/jnr.20696⟩
Journal of Neuroscience Research, Wiley, 2006, 83 (2), pp.233-42. ⟨10.1002/jnr.20696⟩
ISSN: 1097-4547
0360-4012
DOI: 10.1002/jnr.20696
Popis: Oxidative stress has been suggested to be an important mediator of dopaminergic cell death in Parkinson's disease (PD). We investigated the neuroprotective potential of Cu/Zn superoxide dismutase (SOD1) overexpression in the rat substantia nigra (SN) following adenovirus-mediated gene transfer. Human dopaminergic SK-N-SH cells were transduced with adenoviral vectors expressing either human SOD1 (Ad-SOD1) or β-galactosidase (Ad-βgal) before exposure to 1 mM of the 1-methyl-4-phenylpyridinium ion (MPP+). A strong neuroprotective effect of SOD1 gene transfer was observed in the SK-N-SH cells exposed to MPP+ compared with controls. Adult rats were then given unilateral injections of either Ad-SOD1 or Ad-βgal into the striatum, and MPP+ was administered 8 days later at the same location. Strong transgene expression was detected in the SN dopaminergic neurons, a consequence of retrograde axonal transport of the adenoviral particles. The amphetamine-induced rotational behavior of the rats was markedly lower in Ad-SOD1-injected rats than in control animals. Also, behavioral recovery significantly correlated with the number of tyrosine hydrolase-expressing neurons in the SN of the treated rats. These results are consistent with oxidative stress contributing to the MPP+-induced neurodegenerative process. They also indicate that SOD1 gene transfer into the nigrostriatal system may be a potential neuroprotective strategy for treating PD. © 2005 Wiley-Liss, Inc.
Databáze: OpenAIRE
Externí odkaz: