کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5722139 | 1608117 | 2017 | 7 صفحه PDF | دانلود رایگان |
- Dysregulation of basal imidazoline receptors in major depression postmortem brain.
- I1-type IRAS/nischarin (167Â kDa) protein is downregulated by antidepressant drugs.
- I1-type 85Â 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 (167Â kDa) and, for comparison, those of I1- (85Â kDa) and I2- (45Â kDa and 30Â kDa) IR proteins were quantified by western blotting in postmortem prefrontal cortex (PFC/BA9) of antidepressant-free ([MDD(â)], 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(â) and significantly decreased (â24%, p=0.001) in MDD(+), revealing that basal I1-IR content was downregulated by antidepressants. Putative 85Â kDa I1-IR was upregulated (+35%, p=0.035) in MDD(â) but it was not reduced (â14%, 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 85Â kDa IR proteins in PFC/BA9 (control and MDD subjects). In MDD and regardless of antidepressants, the content of cortical 45Â kDa I2-IR was increased (+31%, p=0.006) and that of 30Â kDa I2-IR decreased (â14%, 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.
Journal: Journal of Affective Disorders - Volume 208, 15 January 2017, Pages 646-652