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.
Neurochem Res. 2010 Oct;35(10):1620-7. doi: 10.1007/s11064-010-0222-3. Epub 2010 Jun 26.
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.
本研究旨在通过检测神经化学、行为学和内源性抗氧化谷胱甘肽的改变,比较纹状体内注射脂多糖(LPS)、1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)和 6-羟多巴胺(6-OHDA)对神经的损伤作用。所有结果均在损伤后 1、3 和 7 天收集。LPS 导致纹状体多巴胺的延迟性减少,而高香草酸则在第一个时间点显著增加。相比之下,MPTP 引起多巴胺和高香草酸的减少,分别在 3 天和 7 天出现。而 6-OHDA 则引起多巴胺和高香草酸的初始增加,随后伴随着这种神经递质的后续减少,同时在相同的时间段内多巴胺代谢物也减少。此外,黑质中的谷胱甘肽似乎比 MPTP 或 6-OHDA 对 LPS 更为敏感。行为学数据表明,MPTP 和 6-OHDA 引起了损伤,而 LPS 则没有。综上所述,本研究表明,纹状体内注射 LPS 可能为神经炎症提供新的见解,模拟帕金森病运动前期的特征。