Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases

Quintero-Villegas, Alejandro; Valdés‐Ferrer, Sergio Iván

doi:10.1186/s10020-022-00497-2

Cited by 17 publications

(8 citation statements)

References 119 publications

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“…Moreover, it has been shown that the 5-HT 7 receptor is associated with macrophage M2 polarization, characterized as protective cells in an inflammatory context [ 20 ]. A recent review describes the known protective roles of 5-HT 7 receptors in neurodegenerative diseases that are associated with reduction of oxidative stress, synaptic remodeling, and immunomodulation [ 32 ]. All these reports support our results and the 5-HT 7 receptor ability to modulate immune function in MS and beyond.…”

Section: Discussionmentioning

confidence: 99%

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients

et al. 2022

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Serotonin (5-HT) is known as a potent immune cell modulator in autoimmune diseases and should be protective in the pathogenesis of multiple sclerosis (MS). Nevertheless, there is limited knowledge about receptors involved in 5-HT effects as well as induced mechanisms. Among 5-HT receptors, the 5-HT7 receptor is able to activate naïve T cells and influence the inflammatory response; however, its involvement in the disease has never been studied so far. In this study, we collected blood sample from three groups: acute relapsing MS patients (ARMS), natalizumab-treated MS patients (NTZ), and control subjects. We investigated the 5-HT7 expression on circulating lymphocytes and evaluated the effects of its activation on cytokine production with peripheral blood mononuclear cell (PBMC) cultures. We found a significant increase in the 5-HT7 surface expression on T lymphocytes and on the different CD4+ T cell subsets exclusively in NTZ-treated patients. We also showed that the selective agonist 5-carboxamidotryptamine (5-CT)-induced 5-HT7R activation significantly promotes the production of IL-10, a potent immunosuppressive cytokine in PBMCs. This study provides for the first time a dysregulation of 5-HT7 expression in NTZ-MS patients and its ability to promote IL-10 release, suggesting its protective role. These findings strengthen the evidence that 5-HT7 may play a role in the immuno-protective mechanisms of NTZ in MS disease and could be considered as an interesting therapeutic target in MS.

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Section: Discussionmentioning

confidence: 99%

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients

et al. 2022

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“…5-HT6 receptors are postsynaptic GPCRs located in the corpus striatum, nucleus accumbens, cerebral cortex, amygdala, hippocampus, and hypothalamus ( Figure 2 ) (Quintero-Villegas and Valdés-Ferrer, 2022 ). Recent studies have demonstrated the antidepressant and anxiolytic effects of two specific 5-HT6 receptor agonists in rodents (Carr et al, 2011 ).…”

Section: Serotonin and Its Receptorsmentioning

confidence: 99%

Latest updates on the serotonergic system in depression and anxiety

Lin

Liu

Guan

et al. 2023

Front. Synaptic Neurosci.

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Psychiatric disorders are among the leading causes of global health burden, with depression and anxiety being the most disabling subtypes. The two common disorders, depression and anxiety, usually coexist and are pathologically polygenic with complicated etiologies. Current drug-based therapies include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and 5-hydroxytryptamine partial agonists. However, these modalities share common limitations, such as slow onset and low efficacy, which is why potential mechanistic insights for new drug targets are needed. In this review, we summarize recent advances in brain localization, pathology, and therapeutic mechanisms of the serotonergic system in depression and anxiety.

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“…In addition, a recent study revealed that BDNF and the 5-HT7 receptor also interconnect. Indeed, when activated, these receptors increase the level of BDNF and TrkB affinity [ 100 ]. Interestingly, a study in rodents demonstrated that a single injection of BDNF improved the activity of serotonin transporter in the hippocampus of these animals.…”

Section: Exploring Bdnf and Its Connection To Mood Disordersmentioning

confidence: 99%

BDNF Unveiled: Exploring Its Role in Major Depression Disorder Serotonergic Imbalance and Associated Stress Conditions

2023

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Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a significant role in the survival and development of neurons, being involved in several diseases such as Alzheimer’s disease and major depression disorder. The association between BDNF and major depressive disorder is the subject of extensive research. Indeed, numerous studies indicate that decreased levels of BDNF are linked to an increased occurrence of depressive symptoms, neuronal loss, and cortical atrophy. Moreover, it has been observed that antidepressive therapy can help restore BDNF levels. In this review, we will focus on the role of BDNF in major depression disorder serotonergic imbalance and associated stress conditions, particularly hypothalamic–pituitary–adrenal (HPA) axis dysregulation and oxidative stress. All of these features are highly connected to BDNF signaling pathways in the context of this disease, and exploring this topic will aim to advance our understanding of the disorder, improve diagnostic and treatment approaches, and potentially identify new therapeutic targets to alleviate the heavy burden of depression on society.

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Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases

Cited by 17 publications

References 119 publications

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients

T Lymphocyte Serotonin 5-HT7 Receptor Is Dysregulated in Natalizumab-Treated Multiple Sclerosis Patients

Latest updates on the serotonergic system in depression and anxiety

BDNF Unveiled: Exploring Its Role in Major Depression Disorder Serotonergic Imbalance and Associated Stress Conditions

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