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.
