CD200 attenuates methamphetamine-induced microglial activation and dopamine depletion.
10.1007/s11596-012-0072-0
- Author:
Xia YUE
1
;
Dongfang QIAO
;
Aifeng WANG
;
Xiaohui TAN
;
Yanhong LI
;
Chao LIU
;
Huijun WANG
Author Information
1. Department of Forensic Science, Southern Medical University, Guangzhou, China. yiluyangguang@163.com
- Publication Type:Journal Article
- MeSH:
Animals;
Animals, Newborn;
Antigens, CD;
administration & dosage;
Cells, Cultured;
Coculture Techniques;
Corpus Striatum;
cytology;
drug effects;
immunology;
Cytokines;
immunology;
Dopamine;
immunology;
Drug Interactions;
Male;
Methamphetamine;
toxicity;
Microglia;
drug effects;
immunology;
Neurons;
metabolism;
Rats;
Rats, Sprague-Dawley
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2012;32(3):415-421
- CountryChina
- Language:English
-
Abstract:
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.
