Glucocorticoids in the Physiological and Transcriptional Regulation of 5-HT1A Receptor and the Pathogenesis of Depression

Abstract

There is growing increase in the global prevalence of depression, but treatment outcome of this highly disabling disease is not satisfactory. Many patients are not benefitted by the currently prescribed antidepressants—together with this partial remission is very common. Improving treatment strategies and developing better therapeutic agents for treating depression is therefore highly needed. Stress-related epigenetic changes play a critical role in the pathogenesis as well as treatment of depression. Stressful events activate hypothalamic-pituitary-adrenal axis to increase circulating levels of glucocorticoids (GCs), and a greater sensitivity to this fright and flight response increases risk of depression. A role of serotonin (5-hydroxytryptamine; 5-HT) in responses to stress and in the pathogenesis and treatment of depression is well established. Substantial evidence supports a critical role of 5-HT1A receptors in these effects of 5-HT. The present article targets stress-induced higher and sustained increases of GCs and mediated influences on the physiological as well transcriptional regulation of 5-HT1A receptors to evaluate their causal role in the pathogenesis of depression. It is suggested that synthetic compounds with antagonist activity for GC receptors and agonist activity for 5-HT1A receptors may prove better therapeutic agents for treating depression.

Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature

“…Nevertheless, we have decided to leave these factors in a separate category (because their categorization may not be as immediately clear-cut as others), and these factors include: low-level light [ 429 ], weight cycling [ 430 ], water contaminants [ 431 ], trade [ 432 ], air pollution [ 433 , 434 ], program-level variables (ex. feedback and learning experience) [ 435 ], TV viewing [ 436 ], falls [ 437 ], various other biological factors [ 116 , 136 , 141 , 151 , 164 , 182 , 363 , 364 , 438 , 439 , 440 , 441 , 442 , 443 , 444 , 445 , 446 , 447 , 448 , 449 , 450 , 451 , 452 , 453 , 454 , 455 , 456 , 457 , 458 , 459 , 460 , 461 , 462 , 463 , 464 , 465 , 466 , 467 , 468 , …”

Antidepressant Potential of a Functionalized 3-Selanyl Benzo[b]Furan Compound in Mice: Focus on the Serotonergic System

“…According to Carr et al., mice with a higher density of 5-HT 1A autoreceptors demonstrated enhanced responses to stressors. In addition, it is suggested that synthetic compounds with antagonist activity for glucocorticoid receptors and agonist activity for 5-HT 1A receptors may prove better therapeutic agents for treating depression . Consequently, drugs such as buspirone, a partial agonist for 5-HT 1A receptors, are used clinically to treat mood disorders such as depression and anxiety …”

“…In addition, it is suggested that synthetic compounds with antagonist activity for glucocorticoid receptors and agonist activity for 5-HT 1A receptors may prove better therapeutic agents for treating depression. 37 Consequently, drugs such as buspirone, a partial agonist for 5-HT 1A receptors, are used clinically to treat mood disorders such as depression and anxiety. 38 Results indicated the possible modulation of 5-HT 2A receptors by SeBZF3 since its antidepressant-like effect was impeded by ketanserin, a 5-HT 2A/C receptor antagonist.…”

Graves’ disease as a driver of depression: a mechanistic insight

“…Adrenocortical steroids enter the brain and have widespread effects, particularly impairing hippocampal function ( 86 ). Long-term exposure to the hormone environment can decrease the secretion of derived neurotrophic factor (BDNF) and interfere with neural development ( 87 , 88 ). Adrenocortical hormones not only destroy the plasticity and structure of neurons, but also exert cytotoxic effects by regulating neurotransmitters.…”