Research paperDysregulation of IRAS/nischarin and other potential I1-imidazoline receptors in major depression postmortem brain: Downregulation of basal contents by antidepressant drug treatments

•Dysregulation of basal imidazoline receptors in major depression postmortem brain.•I1-type IRAS/nischarin (167 kDa) protein is downregulated by antidepressant drugs.•I1-type 85 kDa protein is downregulated by antidepressant drugs.

BackgroundMajor depressive disorder (MDD) has been associated with altered brain densities of imidazoline receptors (I1-IR and I2-IR types).MethodsThe contents of potential I1-IR IRAS/nischarin (167 kDa) and, for comparison, those of I1- (85 kDa) and I2- (45 kDa and 30 kDa) IR proteins were quantified by western blotting in postmortem prefrontal cortex (PFC/BA9) of antidepressant-free ([MDD(−)], n=9) and antidepressant-treated ([MDD(+)], n=12) subjects and matched controls (n=19).ResultsIn MDD, regardless of antidepressant treatment (n=21), IRAS/nischarin was not altered in PFC/BA9. However, the content of IRAS/nischarin was found modestly and not significantly increased (+19%, p=0.075) in MDD(−) and significantly decreased (−24%, p=0.001) in MDD(+), revealing that basal I1-IR content was downregulated by antidepressants. Putative 85 kDa I1-IR was upregulated (+35%, p=0.035) in MDD(−) but it was not reduced (−14%, p=0.37) in MDD(+). There was a positive correlation (r=0.33, p=0.037, n=40) between the contents of IRAS/nischarin and 85 kDa IR proteins in PFC/BA9 (control and MDD subjects). In MDD and regardless of antidepressants, the content of cortical 45 kDa I2-IR was increased (+31%, p=0.006) and that of 30 kDa I2-IR decreased (−14%, p=0.002), indicating basal dysregulations of these potential IRs.LimitationsMDD(+) subjects had been treated with a variety of antidepressant drugs. The results must be understood in the context of suicide victims with MDD.ConclusionsThe dysregulation of IRAS/nischarin in depressed brains is a major novel finding that supports a role of this potential I1-IR in the neurobiology of MDD and in the molecular mechanisms of antidepressant drugs.