Function of complement factor H and imaging of small molecules by MALDI-MSI in a methamphetamine behavioral sensitization model

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.

Keywords: Behavioral sensitization model; C1q; Complement factor H; Matrix-assisted laser desorption time of flight ionization mass spectrometry imaging (MALDI–TOF–MSI); Metabolites; Methamphetamine.