Loss of inhibition by brain natriuretic peptide over P2X3 receptors contributes to enhanced spike firing of trigeminal ganglion neurons in a mouse model of familial hemiplegic migraine type-1

Marchenkova, Anna; Maagdenberg, Arn M. J. M. van den; Nistri, Andrea

doi:10.1016/j.neuroscience.2016.06.034

Cited by 18 publications

(20 citation statements)

References 40 publications

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“…The role of ATP in migraine was initially suggested to involve vascular events (see Burnstock and Verkhratsky, 2012 ; Haanes and Edvinsson, 2014 ). Later, P2X3R in nociceptive brain areas, including the thalamus and trigeminal nucleus, were investigated and their interaction with P2Y 1 R in trigeminal neurons ( Hullugundi et al, 2014 ; Marchenkova et al, 2016 ). The therapeutic potential of antagonists to P2X7R for migraine treatment has been proposed ( Gölöncsér and Sperlágh, 2014 ), as well as P2X3R and P2X2/3R antagonists ( Kilinc et al, 2015 ; Yegutkin et al, 2016 ).…”

Section: Disorders Of the Central Nervous System (Cns)mentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

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Section: Disorders Of the Central Nervous System (Cns)mentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

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“…A recent report has shown that trigeminal neurons in WT mice have negative control over P2X3 receptors by brain natriuretic peptide pathway which is reflected in the suppression of P2X3 receptors-mediated excitability. In FHM1 KI cultures, the lack of this inhibition causes a hyperexcitability phenotype which could facilitate the trigeminal pain signaling in migraine [81]. The phenotype of TG neurons sensitization in FHM1 KI mice has been shown to be not due to an up-regulation of CGRP receptors, whereas it is likely caused by larger CGRP release.…”

Section: Molecular Pain Mechanisms Modified Trigeminovascular Procesmentioning

confidence: 99%

Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology

Dehghani

Karataş

2019

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Migraine, an extremely disabling neurological disorder, has a strong genetic component. Since monogenic migraines (resulting from mutations or changes in a single gene) may help researchers discover migraine pathophysiology, transgenic mice models harboring gene mutations identified in Familial Hemiplegic Migraine (FHM) patients have been generated. Studies in these FHM mutant mice models have shed light on the mechanisms of migraine and may aid in the identification of novel targets for treatment. More specifically, the studies shed light on how gene mutations, hormones, and other factors impact the pathophysiology of migraine. The models may also be of relevance to researchers outside the field of migraine as some of their aspects are relevant to pain in general. Additionally, because of the comorbidities associated with migraine, they share similarities with the mutant mouse models of epilepsy, stroke, and perhaps depression. Here, we review the experimental data obtained from these mutant mice and focus on how they can be used to investigate the pathophysiology of migraine, including synaptic plasticity, neuroinflammation, metabolite alterations, and molecular and behavioral mechanisms of pain.

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“…The pellet was resuspended with Neurobasal A (Fisher) containing B27 (2%; Fisher), L-glutamine (0.2%; Fisher), and antibiotic/antimycotic solution (0.1%), and cells were plated onto glass cover slips coated with Poly-D-lysine/Laminin (Fisher). The cells were then incubated at 37°C in a humidified 5% CO 2 chamber, and whole-cell patch-clamp electrophysiology was conducted approximately 24 hours after plating (Chen et al, 2008; Marchenkova et al, 2016).…”

Section: Detailed Methodsmentioning

confidence: 99%

Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1^G93AMouse Model for ALS

Seki¹,

Yamamoto

Quinn³

et al. 2019

Preprint

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Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which motor neurons degenerate resulting in muscle atrophy, paralysis and fatality. Studies using mouse models of ALS indicate a protracted period of disease development with progressive motor neuron pathology, evident as early as embryonic and postnatal stages. Key missing information includes concomitant alterations in the sensorimotor circuit essential for normal development and function of the neuromuscular system. Leveraging unique brainstem circuitry, we showin vitroevidence for reflex circuit-specific postnatal abnormalities in the jaw proprioceptive sensory neurons in the well-studied SOD1G93Amouse. These include impaired and arrhythmic action potential burst discharge associated with a deficit in Nav1.6 Na+channels. However, the mechanoreceptive and nociceptive trigeminal ganglion neurons and the visual sensory retinal ganglion neurons were resistant to excitability changes in age matched SOD1G93Amice. Computational modeling of the observed disruption in sensory patterns predicted asynchronous self-sustained motor neuron discharge suggestive of imminent reflexive defects such as muscle fasciculations in ALS. These results demonstrate a novel reflex circuit-specific proprioceptive sensory abnormality in ALS.Significance StatementNeurodegenerative diseases have prolonged periods of disease development and progression. Identifying early markers of vulnerability can therefore help devise better diagnostic and treatment strategies. In this study, we examined postnatal abnormalities in the electrical excitability of muscle spindle afferent proprioceptive neurons in the well-studied SOD1G93Amouse model for neurodegenerative motor neuron disease, ALS. Our findings suggest that these proprioceptive sensory neurons are exclusively afflicted early in the disease process relative to sensory neurons of other modalities. Moreover, they presented Nav1.6 Na+channel deficiency which contributed to arrhythmic burst discharge. Such sensory arrhythmia could initiate reflexive defects such as muscle fasciculations in ALS as suggested by our computational model.

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Loss of inhibition by brain natriuretic peptide over P2X3 receptors contributes to enhanced spike firing of trigeminal ganglion neurons in a mouse model of familial hemiplegic migraine type-1

Cited by 18 publications

References 40 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology

Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1^G93AMouse Model for ALS

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Loss of inhibition by brain natriuretic peptide over P2X3 receptors contributes to enhanced spike firing of trigeminal ganglion neurons in a mouse model of familial hemiplegic migraine type-1

Cited by 18 publications

References 40 publications

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling: Therapeutic Developments

Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology

Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1G93AMouse Model for ALS

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Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1^G93AMouse Model for ALS