Distribution of 5-HT1F Receptors in Monkey Vestibular and Trigeminal Ganglion Cells

Usman, Habiba O.; Balaban, Carey D.

doi:10.3389/fneur.2016.00173

Cited by 14 publications

(12 citation statements)

References 77 publications

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“…Messenger RNA (mRNA) for the 5-HT 1F receptor was found in human brain, uterine, and mesenteric tissue, but not in heart, kidney, liver, pancreas, spleen, or testes. In situ hybridization showed the presence of mRNA in the cerebral cortex, hippocampus, and dorsal raphe of guinea pig brains [60] and in the guinea pig and human TG [61][62][63]. In other studies, mRNA for 5-HT 1F was detected in human cerebral blood vessels [61], rat meningeal dura mater [64], cerebral cortex, and TG [65].…”

Section: -Ht 1f Receptor Locationmentioning

confidence: 99%

Lasmiditan mechanism of action – review of a selective 5-HT1F agonist

et al. 2020

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Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second-and third-order neuronal signaling may be an important component involved in migraine pain. The activation of several serotonergic receptor subtypes can block the release of CGRP, other neuropeptides, and neurotransmitters, and can relieve the symptoms of migraine. Triptans were the first therapeutics developed for the treatment of migraine, working through serotonin 5-HT 1B/1D receptors. The discovery that the serotonin 1F (5-HT 1F) receptor was expressed in the human trigeminal ganglion suggested that this receptor subtype may have a role in the treatment of migraine. The 5-HT 1F receptor is found on terminals and cell bodies of trigeminal ganglion neurons and can modulate the release of CGRP from these nerves. Unlike 5-HT 1B receptors, the activation of 5-HT 1F receptors does not cause vasoconstriction. The potency of different serotonergic agonists towards 5-HT 1F was correlated in an animal model of migraine (dural plasma protein extravasation model) leading to the development of lasmiditan. Lasmiditan is a newly approved acute treatment for migraine in the United States and is a lipophilic, highly selective 5-HT 1F agonist that can cross the blood-brain barrier and act at peripheral nervous system (PNS) and central nervous system (CNS) sites. Lasmiditan activation of CNS-located 5-HT 1F receptors (e.g., in the trigeminal nucleus caudalis) could potentially block the release of CGRP and the neurotransmitter glutamate, thus preventing and possibly reversing the development of central sensitization. Activation of 5-HT 1F receptors in the thalamus can block secondary central sensitization of this region, which is associated with progression of migraine and extracephalic cutaneous allodynia. The 5-HT 1F receptors are also elements of descending pain modulation, presenting another site where lasmiditan may alleviate migraine. There is emerging evidence that mitochondrial dysfunction might be implicated in the pathophysiology of migraine, and that 5-HT 1F receptors can promote mitochondrial biogenesis. While the exact mechanism is unknown, evidence suggests that lasmiditan can alleviate migraine through 5-HT 1F agonist activity that leads to inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways.

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Section: -Ht 1f Receptor Locationmentioning

confidence: 99%

Lasmiditan mechanism of action – review of a selective 5-HT1F agonist

et al. 2020

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“…3-5 5-hydroxy tryptamine (5-HT) is a kind of important humoral mediator and neurotransmitter, and studies have revealed that 5-HT is closely related to the occurrence and development of migraine. [6][7][8] In addition, the studies on many subtypes of 5-HT have found that 5-HT receptor 6 (5-HTR6) bears a close relationship with the occurrence of pain. [9][10][11] Therefore, in this project, the VM patients were enrolled from our department to detect the polymorphism of 5-HTR6 rs770963777 site with the TaqMan-MGB probe and explore the correlation of 5-HTR6 gene polymorphism with VM, hoping to provide a theoretical support for the genetic polymorphism of VM.…”

Section: Introductionmentioning

confidence: 99%

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Qiu

Wang

et al. 2019

Clinical Laboratory Analysis

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Objective To investigate the correlation of 5‐hydroxy tryptamine receptor 6 (5‐HTR6) gene polymorphism with vestibular migraine (VM). Methods A total of 92 VM patients were enrolled as the observation group, and 100 healthy people receiving physical examinations as the control group. Their general clinical information was collected, and the level of 5‐HT in plasma and the vestibular function test indexes were detected. Moreover, the polymorphism of 5‐HTR6 rs770963777 was detected with the TaqMan‐MGB probe. Results The observation group had a lower level of 5‐HT than the control group (P < .05), and the abnormality rates of the vestibular function tests, including the caloric test, head‐shaking test, and vestibular autorotation test, were obviously higher than those in the control group (P < .01). The comparisons showed that the distribution frequencies of the genotypes and alleles were different between the two groups (P < .05). According to the analysis of the genetic mode, there were differences in recessive and additive modes between the two groups (P < .05), but the dominant mode was not different between the two groups (P > .05). Conclusion The level of 5‐HT and the vestibular function test indexes can serve as the effective indicators for observing VM, and the polymorphism of 5‐HTR6 rs770963777 site is correlated with VM onset.

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“…Vestibular ganglion cells, like trigeminal ganglion cells, express 5‐HT 1B , 5‐HT 1D , and 5‐HT 1F receptors (Fig. ) . Ahn et al found that CGRP and 5‐HT 1F receptors colocalize in the vestibular nuclei .…”

Section: Discussion/observationsmentioning

confidence: 98%

Vestibular Neuroscience for the Headache Specialist

Balaban

Black²,

Silberstein

2019

Headache

Self Cite

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Background.-The vestibular system is a multifaceted, integrative sensory system that is often referred to as the "multi-sensory" sense. There is an extensive literature about the vestibular sensory organs and afferent nerve pathways; however, this rich resource is often unknown to the headache specialist.Aims.-In this review, we highlight the significance of vestibular sensory processing beyond its role in the maintenance of balance. The role of the vestibular system in migraine pathophysiology is emphasized, not just in how it impacts dizziness or nausea, but also in its higher order effects on mood and cognition. How the vestibular system responds to current and new migraine therapies, such as anti-CGRP (calcitonin gene-related peptide) antibodies, is also discussed.Conclusions.-The vestibular system is not just about balance; this should be taken into account by clinicians as they assess their patients' associated non-headache symptoms. There is a co-occurrence of migraine and vestibular-based problems and a confluence of disciplines relevant to vestibular migraine.Abbreviations: 5-HT receptors (5-hydroxytryptamine), (serotonin receptors) class of G protein coupled receptor and ligandgated ion channels. The subscript designations refer to specific receptor types, ATPase adenosine triphosphatase, an enzyme that catalyzes the hydrolysis or decomposition of ATP (adenosine triphosphate) into ADP (adenosine diphosphate) and a free phosphate ion, BOLD fMRI blood oxygen level-dependent functional magnetic resonance imaging, Cav2.1 voltage-dependent calcium channel, c-FOS protein that is often used as an indirect marker of neuronal activity, ICHD-3 International Classification of Headache Disorders, NaKA sodiumpotassium ATPase, SSRI selective serotonin reuptake inhibitor, Substance P neuropeptide that may affect vasodilation, inflammation, pain expression, and other regulated processes, TRPV1 transient receptor potential cation channel subfamily V, member 1, UCP2, 3 mitochondrial uncoupling protein 2 (or 3) HEADACHE CURRENTS Headache CurrentsHeadache Headache Currents mismatch") 20 can result in motion sickness, simulator sickness, and cybersickness. [21][22][23][24][25][26] Other somatic, non-vestibular signals that are involved in balance control and spatial orientation have been reviewed elsewhere 7 Since every tissue in the body has mass (including blood), linear acceleration (including gravity) alters sensory signals from baroreceptors, visceral pressure receptors, and somatic proprioceptors. These multiple sensory inputs simultaneously coordinate motor and autonomic responses during movement and changes in posture, particularly during unusual conditions (eg, swimming underwater). Vestibular Sensory PeripheryBody and head movements produce inertial and gravitational forces that are detected by vestibular sensory organs. 27 Since these organs are embedded in the temporal bone of the skull, the sensory information is "head-referenced." These organs are similar in structure in all vertebrates with jaws. 28 There are...

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Distribution of 5-HT1F Receptors in Monkey Vestibular and Trigeminal Ganglion Cells

Cited by 14 publications

References 77 publications

Lasmiditan mechanism of action – review of a selective 5-HT1F agonist

Lasmiditan mechanism of action – review of a selective 5-HT1F agonist

Correlation of 5‐HTR6 gene polymorphism with vestibular migraine

Vestibular Neuroscience for the Headache Specialist

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