CD200 attenuates methamphetamine-induced microglial activation and dopamine depletion.
This study examined the neuroprotective effect of cluster of differentiation molecule 200 (CD200) against methamphetamine (METH)-induced neurotoxicity. In the in vitro experiment, neuron-microglia cultures were treated with METH (20 μmol/L), METH (20 μmol/L)+CD200-Fc (10 μg/mL) or CD200-Fc (10 μg/mL). Those untreated served as control. Microglia activation expressed as the ratio of MHC-II/CD11b was assessed by flow cytometry. The cytokines (IL-1β, TNF-α) secreted by activated microglia were detected by enzyme-linked immunosorbent assay (ELISA). In the in vivo experiment, 40 SD rats were divided into control, METH, METH+CD200-Fc and CD200-Fc groups at random. Rats were intraperitoneally injected with METH (15 mg/kg 8 times at 12 h interval) in METH group, with METH (administered as the same dose and time as the METH group) and CD200-Fc (1 mg/kg at day 0, 2, 4 after METH injection) in METH+CD200-Fc group, with CD200-Fc (1 mg/kg injected as the same time as the METH+CD200-Fc group) or with physiological saline solution in the control group. The level of striatal dopamine (DA) in rats was measured by high-performance liquid chromatography (HPLC). The microglial cells were immunohistochemically detected for the expression of Iba-1, a marker for microglial activation. The results showed that METH could increase the microglia activation in the neuron-microglia cultures and elevate the secretion of IL-1β and TNF-α, which could be attenuated by CD200-Fc. Moreover, CD200-Fc could partially reverse the striatal DA depletion induced by METH and reduce the number of activated microglia, i.e. Iba-1-positive cells. It was concluded that CD200 may have neuroprotective effects against METH-induced neurotoxicity by inhibiting microglial activation and reversing DA depletion in striatum.
Department of Forensic Science, Southern Medical University, Guangzhou, 510515, China.
Xia
X
Yue
Department of Forensic Science, Southern Medical University, Guangzhou, 510515, China.
Dongfang
D
Qiao
Department of Forensic Science, Southern Medical University, Guangzhou, 510515, China.
Aifeng
A
Wang
Department of Forensic Science, Southern Medical University, Guangzhou, 510515, China.
Xiaohui
X
Tan
Department of Forensic science, Nanchang University, Nanchang, 330006, China.
Yanhong
Y
Li
Guangzhou Criminal Science & Technology Institute, Guangzhou, 510030, China.
Chao
C
Liu
Department of Forensic Science, Southern Medical University, Guangzhou, 510515, China. hjwang@fimmu.com.
Huijun
H
Wang
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000008:administration & dosage*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004298:Dopamine / Q000276:immunology*; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015703:Antigens, CD; D016207:Cytokines; D008694:Methamphetamine; C042739:antigens, CD200; D004298:Dopamine