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.
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.
Behav Brain Res. 2019 May 17;364:233-244. doi: 10.1016/j.bbr.2019.02.002. Epub 2019 Feb 4.
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.
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.
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.
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.
目前，新型毒品冰毒（METH）的危害逐渐超过传统阿片类药物，METH 滥用已成为严重的公共卫生和社会问题。在我们之前的研究中，发现补体因子 H（CFH）在 METH 成瘾患者和大鼠的血清以及大鼠的某些大脑区域中上调。
我们使用 ELISA 和免疫荧光法确认了 METH 行为敏化小鼠模型血清和海马中海洛因变化，并用免疫荧光法检测了海马中 C1q 的表达。我们旨在阐明 CFH 和 C1q 在 METH 成瘾机制中的作用。我们还通过基质辅助激光解吸电离质谱成像（MALDI-MSI）检测了不同小分子在选定脑区（伏隔核、海马和腹侧被盖区）的分布。
CFH 的表达在 METH 行为敏化模型小鼠的血清和海马中上调，与我们之前对条件性位置偏爱大鼠的研究结果一致。相比之下，C1q 在海马的苔藓纤维中急剧减少。MALDI-MSI 的小分子成像结果表明，不同区域的 K、抗氧化剂、神经递质和 ATP 代谢相关分子的水平发生了改变。
这些结果表明补体系统参与了 METH 成瘾的机制，并验证了成瘾过程中存在氧化应激和能量代谢变化。这表明有必要进一步研究上述方面。
