A5051277544- Dermatology and Skin Diseases
- Asthma and respiratory diseases
- Neuropeptides and Animal Physiology
- Urticaria and Related Conditions
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- Axon Guidance and Neuronal Signaling
- Developmental Biology and Gene Regulation
- Neurogenesis and neuroplasticity mechanisms
- Pain Mechanisms and Treatments
- Neurotransmitter Receptor Influence on Behavior
- Lipid Membrane Structure and Behavior
- Mast cells and histamine
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Nerve injury and regeneration
Washington University in St. Louis
2003-2021
University of Washington
2021
Itch and pain are two distinct sensations. Although our previous study suggested that gastrin-releasing peptide receptor (GRPR) is an itch-specific gene in the spinal cord, a long-standing question of whether there separate neuronal pathways for itch remains unsettled. We selectively ablated lamina I neurons expressing GRPR cord mice. These mice showed profound scratching deficits response to all itching (pruritogenic) stimuli tested, irrespective their histamine dependence. In contrast,...
Abstract Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role GRP in sensory neurons, we generated floxed Grp mouse line. We found that conditional knockout results attenuated without impairing histamine-induced itch. Using -Cre knock-in line, show upper epidermis skin is exclusively innervated by fibers, whose activation via optogeneics and...
A key question in our understanding of itch coding mechanisms is whether relayed by dedicated molecular and neuronal pathways. Previous studies suggested that gastrin-releasing peptide (GRP) an itch-specific neurotransmitter. Neuromedin B (NMB) a mammalian member the bombesin family peptides closely related to GRP, but its role unclear. Here, we show deficits mice lacking NMB or GRP are non-redundant Nmb/Grp double KO (DKO) displayed additive deficits. Furthermore, both Nmbr/Grpr DKO...
The differentiation and migration of superficial dorsal horn neurons subsequent ingrowth cutaneous afferents are crucial events in the formation somatosensory circuitry spinal cord. We report that regulated by LIM homeobox gene Lmx1b, its downstream targets Rnx Drg11, two transcription factors implicated development circuitry. An analysis Lmx1b mutants shows normally acts to maintain expression Ebf genes repress Zic genes. also exhibit disruption afferent ingrowth, suggesting cells might...
There are substantial disagreements about the expression of gastrin-releasing peptide (GRP) in sensory neurons and whether GRP antibody cross-reacts with substance P (SP). These concerns necessitate a critical revaluation using additional approaches. Here, we show that widely used specifically recognizes but not SP. In spinal cord mice lacking SP (Tac1 KO), only also other peptides, notably neuropeptide Y (NPY), is significantly diminished. We detected Grp mRNA dorsal root ganglias reverse...
Little is known about the molecular mechanisms underlying formation of principal sensory nucleus (PrV) trigeminal nerve, a major relay station for somatotopic pattern in system. Here, we show that mice lacking Drg11, homeodomain transcription factor, exhibit defects within PrV, which include an aberrant distribution Drg11-/- cells, altered expression marker, unusual projections primary afferents from ganglion and, subsequently, increased cell death. In addition, surviving PrV cells delayed...
Pain is comprised of the sensory and affective components. Compared to well-investigated mechanisms pain, much less known about underlying pain. In recent years, accumulating evidence suggests that anterior cingulate cortex (ACC) a key structure for pain affection. To identify molecules may be involved in component we have searched Allen Brain Atlas expression database genes whose enriched ACC, found P311, an 8-kDa peptide, showed strong ACC. P311 also expressed other areas associated with...
Histamine-dependent and -independent itch is conveyed by parallel peripheral neural pathways that express gastrin-releasing peptide (GRP) neuromedin B (NMB), respectively, to the spinal cord of mice. B-type natriuretic (BNP) has been proposed transmit both types via its receptor NPRA encoded Npr1 . However, BNP also binds cognate receptor, NPRC Npr3 with equal potency. Moreover, peptides (NP) signal through G i -couped inhibitory cGMP pathway supposed inhibit neuronal activity, raising...
Abstract B-type natriuretic peptide (BNP) binds to its two cognate receptors NPRA and NPRC, encoded by Npr1 Npr3 , respectively, with equal potency both are expressed in the spinal cord. Moreover, peptides (NP) signal through inhibitory cGMP pathway, raising question of how BNP may transmit itch information. We report that is highly restricted laminae I-II dorsal horn, partially overlaps neuromedin B receptor (NMBR) encodes histaminergic itch. Functional studies indicate NPRC required for...
Natriuretic peptide (NP) family comprises multiple peptides/receptors whose respective role in itch transmission remains unclear. We report that about 23% of Npr1 encodes NP receptor A (NPRA) the superficial spinal cord co-express gastrin-releasing (Grp), while Npr3 C (NPRC), partially overlaps with neuromedin B (NMBR) required for histamine-evoked itch. While is chloroquine- (CQ) and itch, limited to latter. Notably, B-type natriuretic (BNP) significantly facilitated NMB-, but not GRP-,...