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

Benjamin Keller, Jesús A García-Sevilla

Journal of affective disorders 2017 Jan 15

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Major depressive disorder (MDD) has been associated with altered brain densities of imidazoline receptors (I1-IR and I2-IR types). The contents of potential I1-IR IRAS/nischarin (167kDa) and, for comparison, those of I1- (85kDa) and I2- (45kDa and 30kDa) 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). In 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 85kDa 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 85kDa IR proteins in PFC/BA9 (control and MDD subjects). In MDD and regardless of antidepressants, the content of cortical 45kDa I2-IR was increased (+31%, p=0.006) and that of 30kDa I2-IR decreased (-14%, p=0.002), indicating basal dysregulations of these potential IRs. MDD(+) subjects had been treated with a variety of antidepressant drugs. The results must be understood in the context of suicide victims with MDD. The 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. Copyright © 2016 Elsevier B.V. All rights reserved.

Citation

Benjamin Keller, Jesús A García-Sevilla. Dysregulation of IRAS/nischarin and other potential I1-imidazoline receptors in major depression postmortem brain: Downregulation of basal contents by antidepressant drug treatments. Journal of affective disorders. 2017 Jan 15;208:646-652