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

• Published in: Journal of affective disorders Vol. 208; pp. 646 - 652
• Main Authors: Keller, Benjamin, García-Sevilla, Jesús A.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.01.2017
• Subjects: Antidepressant drugs; Imidazoline receptors; IRAS/nischarin; Major depressive disorder; Postmortem human brain; Psychiatry; Imidazoline receptors; Postmortem human brain; IRAS/nischarin; Major depressive disorder; Antidepressant drugs
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2016.10.007

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