Abstract
Manganese (Mn) is an essential trace element. It is known to have various functions, such as participating in enzymatic synthesis, and promoting hematopoiesis. On the other hand, it can cause toxic injury upon excess intake. However, toxic effects and its mechanism on glial cells are unclear. In the present study, we demonstrated that MnCl2 can activate microglia, and that this can cause dopaminergic neuronal injury. Investigation of the underlying mechanisms showed that inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) was induced and highly expressed following Mn treatment. Moreover, pretreatment with S-methylisothiourea (SMT. iNOS inhibitor), Mn-induced iNOS expression and dopaminergic neuronal injury were partly reverse. Pretreatment with minocycline (microglia activation inhibitor), Mn-induced activation of microglia and dopaminergic neuronal injury was partly reverse. Taken together, our results showed that Mn can cause microglia activation, which can up-regulate the level of IL-1β, TNF-α and iNOS, and these inflammatory factors can cause dopaminergic neuronal injury. SMT and minocycline prevent Mn-induced dopaminergic neuronal injury.
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Abbreviations
- Mn:
-
Manganese
- PD:
-
Parkinson’s disease
- CNS:
-
Central nervous system
- NO:
-
Nitric oxide
- TNF-α:
-
Tumor necrosis factor-α
- IL-1β:
-
Interleukin-1β
- GM-CSF:
-
Granulocyte-macrophage colony-stimulating factor
- SD-rats:
-
Sprague-Dawley rats
- SMT:
-
S-methylisothiourea
- TH:
-
Tyrosine hydroxylase
- DMEM/F12:
-
Dulbecco’s modified eagle medium:Nutrient mixture F-12(Ham)(1:1)
- FBS:
-
Fetal bovine serum
- BSA:
-
Bovine serum albumin
- iNOS:
-
Inducible nitric oxide synthase
- IFN-γ:
-
Interferon gamma
- SN:
-
Substantia nigra
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Acknowledgment
This work was supported by National Natural Science Foundation of China Grant #30571545 (WL), #30471434 (WL), and #30771768 (JC).
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Mingchao Liu and Tongjian Cai contributed equally to this work.
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Liu, M., Cai, T., Zhao, F. et al. Effect of Microglia Activation on Dopaminergic Neuronal Injury Induced by Manganese, and Its Possible Mechanism. Neurotox Res 16, 42–49 (2009). https://doi.org/10.1007/s12640-009-9045-x
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DOI: https://doi.org/10.1007/s12640-009-9045-x