Differential cAMP levels and serotonin effects in blood peripheral mononuclear cells and lymphocytes from major depression patients

doi:10.1016/j.intimp.2004.05.001

Cited by 18 publications

(6 citation statements)

References 27 publications

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“…As downstream proteins of the 5-HT1AR pathway, we found that p-CREB and p-PKA in the hippocampus were upregulated due to the 5-HT1AR agonist-like effects of KL. Similar results have been reported regarding deficits of hippocampal CA1 5-HT1AR being connected to disturbances of cAMP/PKA/CREB signaling [41–43]. Therefore, we reasonably assumed that the administration of lignan extracts might activate the 5-HT1AR protein, subsequently impacting the expression of downstream proteins.…”

Section: Discussionsupporting

confidence: 87%

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

Zheng

Feng

et al. 2015

PLoS ONE

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Objectives Kadsura longipedunculata (KL) has been widely used for the treatment of insomnia in traditional Chinese medicine. The aim of this study was to explore the mechanism of the sedative and hypnotic effects of KL.Materials and MethodsThe content of KL was evaluated by HPLC-TOF-MS, and a potential target was found and used to construct its 3D structure to screen for potential ligands among the compounds in KL by using bioinformatics analysis, including similarity ensemble approach (SEA) docking, homology modeling, molecular docking and ligand-based pharmacophore. The PCPA-induced insomnia rat model was then applied to confirm the potential targets related to the sedative effects of KL by performing the forced swimming test (FST), the tail suspension test (TST) and the measurement of target-related proteins using western blotting and immunofluorescence.ResultsBioinformatics analysis showed that most of lignan compounds in KL were optimal ligands for the 5-HT1A receptor (5-HT1AR), and they were found to be potential targets related to sedative effects; the main lignan content of KL extracts was characterized by HPLC-TOF-MS, with 7 proposed lignans detected. Administration of KL could significantly reduce FST and TST immobility time in the PCPA-induced 5HT-depleted insomnia rat model. The expressions of proteins related to the 5-HT1AR pathway were regulated by extracts of KL in a concentration-dependent manner, indicating that extracts of KL had 5-HT1AR agonist-like effects.Conclusion In silico analysis and experimental validation together demonstrated that lignan extracts from KL can target 5-HT1AR in insomniac rats, which could shed light on its use as a potential 5-HT1AR agonist drug.

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Section: Discussionsupporting

confidence: 87%

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

Zheng

Feng

et al. 2015

PLoS ONE

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“…A wide range of cytokine-producing cells constitutively express cortisol and the serotonin receptors 5-HT 1A, 5-HT 2A, 5-HT 1B, and 5-HT 3 [29, 45, 46]. Serotonin receptors activate cAMP-dependent pathways and mediate synthesis and release of cytokines and cellular proliferation [9].…”

Section: Discussionmentioning

confidence: 99%

“…Studies of dexamethasone have reported alterations in GR in leukocytes of depressed patients, such as decreased nuclear translocation [47] and cellular proliferation [48]. In addition, lymphocytes from MDD patients have a lower density of 5-HTT [49] and impaired 5-HT 1A receptor functions [45, 46]. …”

Section: Discussionmentioning

confidence: 99%

Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

Hernández

Mendieta

Pérez-Tapia

et al. 2013

Clinical and Developmental Immunology

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Major depressive disorder (MDD) is a psychiatric illness that presents as a deficit of serotonergic neurotransmission in the central nervous system. MDD patients also experience alterations in cortisol and cytokines levels. Treatment with selective serotonin reuptake inhibitors (SSRIs) is the first-line antidepressant regimen for MDD. The aim of this study was to determine the effect of a combination of SSRIs and an immunomodulator—human dialyzable leukocyte extract (hDLE)—on cortisol and cytokines levels. Patients received SSRIs or SSRIs plus hDLE. The proinflammatory cytokines IL-1β, IL-2, and IFN-γ; anti-inflammatory cytokines IL-13 and IL-10; and 24-h urine cortisol were measured at weeks (W) 0, 5, 20, 36, and 52 of treatment. The reduction in cortisol levels in the SSRI-treated group was 30% until W52, in contrast, the combined treatment induced a 54% decrease at W36. The decline in cortisol in patients who were treated with SSRI plus hDLE correlated with reduction of anti-inflammatory cytokines and increases levels of proinflammatory cytokines at the study conclusion. These results suggest that the immune-stimulating activity of hDLE, in combination with SSRIs, restored the pro- and anti-inflammatory cytokine balance and cortisol levels in depressed patients versus those who were given SSRIs alone.

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“…Providing a direct link between 5-HT system function, MDD and monocytes, the 5-HT/5-HIAA ratio in DCs is lower in those suffering from MDD than in their nondepressed counterparts . Monocytes appear to be the primary immunocyte that exhibits alterations in SERT expression in the context of MDD, and further the total number of monocytes expressing SERT has been shown to be reduced in those suffering from MDD . Plausibly, the elevations of proinflammatory cytokines present in certain populations of patients suffering from MDD may act systemically to alter the regulation of 5-HT in peripheral immune cells.…”

Section: -Ht and Peripheral Immune System Functionmentioning

confidence: 99%

Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery

Robson

Quinlan

Blakely

2017

ACS Chem. Neurosci.

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Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

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Differential cAMP levels and serotonin effects in blood peripheral mononuclear cells and lymphocytes from major depression patients

Cited by 18 publications

References 27 publications

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists

Effect of Selective Serotonin Reuptake Inhibitors and Immunomodulator on Cytokines Levels: An Alternative Therapy for Patients with Major Depressive Disorder

Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery

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