Effect of microglia activation on dopaminergic neuronal injury induced by manganese, and its possible mechanism.
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 MnCl(2) 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-alpha (TNF-alpha), interleukin-1beta (IL-1beta) 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-1beta, TNF-alpha and iNOS, and these inflammatory factors can cause dopaminergic neuronal injury. SMT and minocycline prevent Mn-induced dopaminergic neuronal injury.
Liu
Mingchao
M
Department of Occupational & Environmental Health, School of Public Health, Fourth Military Medical University, 17 Changlexi Road, Xi'an, 710032, China.
Cai
Tongjian
T
Zhao
Fang
F
Zheng
Gang
G
Wang
Qiang
Q
Chen
Yaoming
Y
Huang
Chuanshu
C
Luo
Wenjing
W
Chen
Jingyuan
J
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D018920:Coculture Techniques / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D017895:Manganese Compounds; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008911:Minocycline / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D002712:Chlorides; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D017895:Manganese Compounds; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D007550:Isothiuronium; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase; C027744:S-methylisothiopseudouronium; D008911:Minocycline; C025340:manganese chloride; D004298:Dopamine