Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The developmental mechanism that contributes to the highly organized axonal connections within the cerebral cortex is not well understood. This is partly due to the lack of molecular markers specifically expressed in corticocortical associative neurons during the period of circuit formation. We have shown previously that latexin, a carboxypeptidase A inhibitor, is expressed in intrahemispheric corticocortical neurons from the second postnatal week in the rat (Arimatsu et al. [1999] Cereb. Cortex 9:569-576). In the present study, we first demonstrate in the adult rat that the orphan nuclear receptor Nurr1 is coexpressed in latexin-expressing neurons located in layer V, sublayer VIa, and the white matter of the lateral sector of the neocortex, and also in latexin-negative early born neurons in sublayer VIb of the entire neocortex. Virtually all Nurr1-expressing neurons exhibit immunoreactivity for phosphate-activated glutaminase but not for gamma-aminobutyric acid, suggesting that they are glutamatergic-excitatory neurons. By combining Nurr1 immunohistochemistry and 5-bromo-2'-deoxyuridine-birthdating, we then show that Nurr1 is expressed in (early born) subplate neurons and (later born) presumptive latexin-expressing neurons from embryonic day 18 onward. Finally, by combination of Nurr1 immunohistochemistry and retrograde tracing, we show that Nurr1-expressing neurons, including those in sublayer VIb, contribute predominantly to long-range intrahemispheric corticocortical projections. These results raise the possibility that Nurr1 plays a role in the establishment and maintenance of normal corticocortical circuitry and function.
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PMID:Organization and development of corticocortical associative neurons expressing the orphan nuclear receptor Nurr1. 1452 47

Serotonin (5-HT) is involved in neuroimmunomodulation. We analyzed the effects of sumatriptan, a 5-HT(1B/1D) receptor agonist, and ondansetron, a 5-HT(3) receptor antagonist, on thalamic mast cell (TMC) population, the only immunocytes known to infiltrate the brain in physiological conditions. Only sumatriptan was effective, significantly increasing TMC numbers versus controls, and especially those containing 5-HT. 5-HT(1B) receptors are concentrated in the median eminence on non-serotonergic axonal endings, probably hypothalamic terminal fibers, involved in hypothalamic-pituitary neuroendocrine modulating processes. TMC variations could reflect serotonergic actions on these fibers. TMCs would thus be cellular interfaces mediating immune action in the nervous system in relation with the hormonal status of the organism.
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PMID:Evidence for serotonin influencing the thalamic infiltration of mast cells in rat. 1565 99

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions.
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PMID:Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons. 2928 23

Neuroinflammation is a recognized pathogenic mechanism underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but the inflammatory mechanisms influencing peripheral motor axon degeneration remain largely unknown. A recent report showed a pathogenic role for c-Kit-expressing mast cells mediating inflammation and neuromuscular junction denervation in muscles from SOD1G93A rats. Here, we have explored whether mast cells infiltrate skeletal muscles in autopsied muscles from ALS patients. We report that degranulating mast cells were abundant in the quadriceps muscles from ALS subjects but not in controls. Mast cells were associated with myofibers and motor endplates and, remarkably, interacted with neutrophils forming large extracellular traps. Mast cells and neutrophils were also abundant around motor axons in the extensor digitorum longus muscle, sciatic nerve, and ventral roots of symptomatic SOD1G93A rats, indicating that immune cell infiltration extends along the entire peripheral motor pathway. Postparalysis treatment of SOD1G93A rats with the tyrosine kinase inhibitor drug masitinib prevented mast cell and neutrophil infiltration, axonal pathology, secondary demyelination, and the loss of type 2B myofibers, compared with vehicle-treated rats. These findings provide further evidence for a yet unrecognized contribution of immune cells in peripheral motor pathway degeneration that can be therapeutically targeted by tyrosine kinase inhibitors.
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PMID:Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. 3028 15

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by extensive inflammation, demyelination, axonal loss and gliosis. Evidence indicates that mast cells contribute to immunopathogenesis of both MS and experimental autoimmune encephalomyelitis (EAE), which is the most employed animal model to study this disease. Considering the inflammatory potential of mast cells, their presence at the CNS and their stabilization by certain drugs, we investigated the effect of ketotifen fumarate (Ket) on EAE development. EAE was induced in C57BL/6 mice by immunization with MOG35-55 and the animals were injected daily with Ket from the seventh to the 17th day after disease induction. This early intervention with Ket significantly reduced disease prevalence and severity. The protective effect was concomitant with less NLRP3 inflammasome activation, rebalanced oxidative stress and also reduced T cell infiltration at the CNS. Even though Ket administration did not alter mast cell percentage at the CNS, it decreased the local CPA3 and CMA1 mRNA expression that are enzymes typically produced by these cells. Evaluation of the CNS-barrier permeability indicated that Ket clearly restored the permeability levels of this barrier. Ket also triggered an evident lymphadenomegaly due to accumulation of T cells that produced higher levels of encephalitogenic cytokines in response to in vitro stimulation with MOG. Altogether these findings reinforce the concept that mast cells are particularly relevant in MS immunopathogenesis and that Ket, a known stabilizer of their activity, has the potential to be used in MS control.
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PMID:Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy? 3146 82


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