Lipopolysaccharide preconditioning induces protection against lipopolysaccharide-induced neurotoxicity in organotypic midbrain slice culture

被引：21
作者：
Ding Y. [1 ]
Li L. [1 ]
机构：
[1] Department of Pathology, Capital Medical University
来源：
Neuroscience Bulletin | 2008年 / 24卷 / 4期
关键词：
Dopaminergic neurons; Inflammation; Lipopolysaccharide; Microglia; Neuroprotection; Organotypic midbrain slice culture; Preconditioning; Tumor necrosis factor-α;
D O I：
10.1007/s12264-008-0408-8
中图分类号：
学科分类号：
摘要：
Objective: To identify the protective effect of lipopolysaccharide (LPS) preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms. Methods: After cultured in vitro for 14 d, the rat organotypic midbrain slices were pretreated with different concentrations (0, 1, 3, 6 or 10 ng/mL) of LPS for 24 h followed by treatment with 100 ng/mL LPS for 72 h. The whole slice viability was determined by measurement of the activity of lactic acid dehydrogenase (LDH). Tyrosine hydroxylase-immunoreactive (TH-IR) neurons and CD11b/c equivalent-immunoreactive (OX-42-IR) microglia in the slices were observed by immunohistochemical method, and tumor necrosis factor-α (TNF-α) levels in the culture media were detected by enzymelinked immunosorbent assays (ELISA). Results: In the slices treated with 100 ng/mL LPS for 72 h, the number of TH-IR neurons reduced from 191±12 in the control slices to 46±4, and the LDH activity elevated obviously (P < 0.01), along with remarkably increased number of OX-42-IR cells and production of TNF-α (P < 0.01). Preconditioning with 3 or 6 ng/mL LPS attenuated neuron loss (the number of TH-IR neurons increased to 126±12 and 180±13, respectively) and markedly reduced LDH levels (P < 0.05), accompanied by significant decreases of OX-42-IR microglia activation and TNF-α production (P < 0.05). Conclusion: Low-dose LPS preconditioning could protect dopaminergic neurons against inflammatory damage in rat midbrain slice culture, and inhibition of microglial activation and reduction of the proinflammatory factor TNF-α production may contribute to this protective effect. Further understanding the underlying mechanism of LPS preconditioning may open a new window for treatment of Parkinson's disease. © 2008 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag GmbH.
引用
收藏
页码：209 / 218
页数：9
相关论文
共 38 条
  • [1] Blandini F., Nappi G., Tassorelli C., Martignoni E., Functional changes of the basal ganglia circuitry in Parkinson's disease, Prog Neurobiol, 62, pp. 63-88, (2000)
  • [2] McGeer P.L., Itagaki S., Boyes B.E., McGeer E.G., Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains, Neurology, 38, pp. 1285-1291, (1988)
  • [3] Vila M., Jackson-Lewis V., Guegan C., Wu D., Teismann P., Choi D., Et al., The role of glial cells in Parkinson's disease, Curr Opin Neurol, 14, pp. 483-489, (2001)
  • [4] Boka G., Anglade P., Wallach D., Javoy-Agid F., Agid Y., Hirsch E.C., Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease, Neurosci Lett, 172, pp. 151-154, (1994)
  • [5] Nagatsu T., Mogi M., Ichinose H., Togari A., Cytokines in Parkinson's disease, J Neural Transm Suppl, 58, pp. 143-151, (2000)
  • [6] Czlonkowska A., Kurkowska-Jastrzebska I., Czlonkowski A., Peter D., Stefano G.B., Immune processes in the pathogenesis of Parkinson's disease-a potential role for microglia and nitric oxide, Med Sci Monit, 8, pp. 165-177, (2002)
  • [7] Wyss-Coray T., Mucke L., Inflammation in neurodegenerative disease-a double-edged sword, Neuron, 35, pp. 419-432, (2002)
  • [8] Nguyen M.D., Julien J.P., Rivest S., Innate immunity: The missing link in neuroprotection and deurodegeneration?, Nat Rev Neurosci, 3, pp. 216-227, (2002)
  • [9] Lehnardt S., Massillon L., Follett P., Jensen F.E., Ratan R., Rosenberg P.A., Et al., Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway, Proc Natl Acad Sci USA, 100, pp. 8514-8519, (2003)
  • [10] Herrera A.J., Castano A., Venero J.L., Cano J., MacHado A., The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system, Neurobiol Dis, 7, pp. 429-447, (2000)
1234