Jiamin Xu1, Zhilin Zhang1, Runzhe Liu1, Yi Sun1, Huihui Liu2, Zongxiu Nie3, Xin Zhao1, Xiaoping Pu4. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. 2. Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China; Beijing National Laboratory for Molecular Sciences, Beijing 100190, China. 3. Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, China; Beijing National Laboratory for Molecular Sciences, Beijing 100190, China; Beijing Center for Mass Spectrometry, Beijing 100190, China. 4. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: pxp123@bjmu.edu.cn.
Abstract
BACKGROUND: At present, the harm of new-type drug, methamphetamine (METH), has gradually exceeded that of the traditional opioid drugs, and METH abuse has become a serious public health and social problem. In our previous study, complement factor H (CFH) was found to be upregulated in the sera of METH-addicted patients and rats and in certain brain regions in the rats. METHODS: We used ELISA and immunofluorescence to confirm the changes in CFH in the serum and hippocampus of a METH behavioral sensitization mouse model, and C1q expression was also detected by immunofluorescence in the hippocampus. We aimed to elucidate the involvement of CFH and C1q in the mechanism of METH addiction. We also detected the distribution of various small molecules by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in select brain regions: the nucleus accumbens, the hippocampus and the ventral tegmental area. RESULTS: The expression of CFH was upregulated in the serum and hippocampus of METH behavioral sensitization model mice, consistent with our previous research on conditioned place preference rats. In contrast, C1q decreased dramatically in the mossy fibers of the hippocampus. The results of small-molecule imaging by MALDI-MSI showed that the levels of K+, antioxidants, neurotransmitters, and ATP metabolism-related molecules were altered in different regions. CONCLUSIONS: These results indicate the involvement of the complement system in the mechanism of METH addiction and validate the presence of oxidative stress, energy metabolism changes during addiction. This suggests the utility of further investigation into the above aspects.
BACKGROUND: At present, the harm of new-type drug, methamphetamine (METH), has gradually exceeded that of the traditional opioid drugs, and METH abuse has become a serious public health and social problem. In our previous study, complement factor H (CFH) was found to be upregulated in the sera of METH-addicted patients and rats and in certain brain regions in the rats. METHODS: We used ELISA and immunofluorescence to confirm the changes in CFH in the serum and hippocampus of a METH behavioral sensitization mouse model, and C1q expression was also detected by immunofluorescence in the hippocampus. We aimed to elucidate the involvement of CFH and C1q in the mechanism of METH addiction. We also detected the distribution of various small molecules by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in select brain regions: the nucleus accumbens, the hippocampus and the ventral tegmental area. RESULTS: The expression of CFH was upregulated in the serum and hippocampus of METH behavioral sensitization model mice, consistent with our previous research on conditioned place preference rats. In contrast, C1q decreased dramatically in the mossy fibers of the hippocampus. The results of small-molecule imaging by MALDI-MSI showed that the levels of K+, antioxidants, neurotransmitters, and ATP metabolism-related molecules were altered in different regions. CONCLUSIONS: These results indicate the involvement of the complement system in the mechanism of METH addiction and validate the presence of oxidative stress, energy metabolism changes during addiction. This suggests the utility of further investigation into the above aspects.