Intranigral LPS administration produces dopamine, glutathione but not behavioral impairment in comparison to MPTP and 6-OHDA neurotoxin models of Parkinson's disease.
The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre-motor phase of Parkinson's disease.
Ariza
Deborah
D
Departamento de Farmacologia, Universidade Federal do Paraná, Setor de Ciências Biológicas, Av. Francisco H. dos Santos s/n, CEP: 81.531-990, Caixa Postal: 19031, Curitiba, PR, Brazil.
Lima
Marcelo M S
MM
Moreira
Camila G
CG
Dombrowski
Patrícia A
PA
Avila
Thiago V
TV
Allemand
Alexandra
A
Mendes
Daniel A G B
DA
Da Cunha
Claudio
C
Vital
Maria A B F
MA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000523:psychology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra; D013997:Time Factors
D008070:Lipopolysaccharides; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005978:Glutathione; D004298:Dopamine