Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase A
| Autor: | Elaine Sanders-Bush, David A. Lewis, Manier Dh, Richard C. Shelton |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Prefrontal Cortex Poison control CREB Article Young Adult Sex Factors Internal medicine Humans Medicine Receptor Serotonin 5-HT2A Protein kinase A Receptor Protein Kinase C Protein kinase C 5-HT receptor Aged Depressive Disorder Major biology business.industry Kinase General Neuroscience Age Factors Middle Aged Cyclic AMP-Dependent Protein Kinases Endocrinology Gene Expression Regulation Postmortem Changes biology.protein Tetradecanoylphorbol Acetate Female Serotonin business |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| Popis: | Previous human postmortem brain tissue research has implicated abnormalities of 5-HT receptor availability in depression and suicide. Although altered abundance of 5-HT 1A, 5-HT 2A, and 5-HT 2C receptors (5-HT(1A), 5-HT(2A), and 5-HT(2C)) has been reported, the causes remain obscure. This study evaluated the availability of these three receptor subtypes in postmortem brain tissue specimens from persons with a history of major depression (MDD) and normal controls and tested the relationships to protein kinases A and C (PKA, PKC). Samples were obtained from postmortem brain tissue (Brodmann area 10) from 20 persons with a history of MDD and 20 matched controls as determined by a retrospective diagnostic evaluation obtained from family members. Levels of 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor were quantitated via Western blot analyses. Basal and stimulated PKA and PKC activity were also determined. The depressed samples showed significantly increased 5-HT(2A) receptor abundance relative to controls, but no differences in 5-HT(1A) or 5-HT(2C) receptors. Basal and cyclic AMP-stimulated PKA activity was also reduced in the depressed sample; PKC activity was not different between groups. 5-HT(2A) receptor availability was significantly inversely correlated with PKC activity in controls, but with PKA activity in the depressed sample. Increased 5-HT(2A) receptor abundance and decreased PKA activity in the depressed sample are consistent with prior reports. The correlation of 5-HT(2A) receptor levels with PKA activity in the depressed group suggests that abnormalities of 5-HT(2A) receptor abundance may depend on receptor uncoupling and heterologous regulation by PKA. |
| Databáze: | OpenAIRE |
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