Role of hepatic microsomal oxidation in regulation of monoamine oxidase mediated processes in rat brain (727.1)

Monoamine oxidase (MAO) plays a key role in metabolism of biogenic amines and serves as a marker of alcoholism and depressive disorders. Various isoforms of cytochrome This study was focused on the relationship between MAO activity and hepatic content of cytochrome P450 which reflects the state of microsomal oxidation. Methods. For vital integrative evaluation of hepatic microsomal oxidation in rats, the hexobarbital sleep test was used. Content of cytochrome P450 was measured in hepatic microsomes. Activities of MAO‐A and MAO‐B were measured in the whole brain and brain structures. Content of serotonin, a MAO substrate was measured in the brain and plasma. Intensity of oxidative stress was evaluated by measuring lipid peroxidation products and carbonylated proteins in brain. Results. Rats with short hexibarbital sleep time (SHST) had higher content of microsomal cytochrome P450 than rats with long hexobarbital sleep time (LHST). Whole brain MAO‐A and MAO‐B activities, serotonin and carbonylated protein levels were higher in SHST than LHST rats. MAO‐A and MAO‐B activities were higher in brain cortex of SHST rats; only MAO‐A activity was higher in hypothalamus and medulla of LHST. The same brain regions of LHST rats had higher concentrations of carbonylated proteins and lipid peroxidation products. Conclusion. Data obtained in this study showed a correlation between MAO activity and microsomal oxidation phenotype. Rats with higher hepatic content of cytochrome P450 had higher activities of MAO‐A and MAO‐B in the brain and higher plasma serotonin levels than rats with lower microsomal oxidation. These correlations may reflect contribution of biogenic amines to regulation of cytochrome P450‐dependent monooxygenases and a role of cytochrome P450 in metabolism of biogenic amines and hormones regulating MAO activity including glucocorticoids Grant Funding Source : Russian Foundation for Basic Research grant 11‐04‐01378‐а&14‐04‐01381‐a