31 research outputs found
Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCγ, PKC, and PI3K/Akt pathways during colitis
Background Spinal central sensitization is an important process in the generation and maintenance of visceral hypersensitivity. The release of brain-derived neurotrophic factor (BDNF) from the primary afferent neurons to the spinal cord contributes to spinal neuronal plasticity and increases neuronal activity and synaptic efficacy. The N-Methyl-D-aspartic acid (NMDA) receptor possesses ion channel properties, and its activity is modulated by phosphorylation of its subunits including the NMDA receptor 1 (NR1). Methods Colonic inflammation was induced by a single dose of intracolonic instillation of tri-nitrobenzene sulfonic acid (TNBS). NR1 phosphorylation by BDNF in vivo and in culture was examined by western blot and immunohistochemistry. Signal transduction was studied by direct examination and use of specific inhibitors. Results During colitis, the level of NR1 phospho-Ser896 was increased in the dorsal horn region of the L1 and S1 spinal cord; this increase was attenuated by injection of BDNF neutralizing antibody to colitic animals (36 μg/kg, intravenous (i.v.)) and was also reduced in BDNF+/− rat treated with TNBS. Signal transduction examination showed that the extracellular signal-regulated kinase (ERK) activation was not involved in BDNF-induced NR1 phosphorylation. In contrast, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway mediated BDNF-induced NR1 phosphorylation in vivo and in culture; this is an additional pathway to the phospholipase C-gamma (PLCγ) and the protein kinase C (PKC) that was widely considered to phosphorylate NR1 at Ser896. In spinal cord culture, the inhibitors to PLC (U73122), PKC (bisindolylmaleimide I), and PI3K (LY294002), but not MEK (PD98059) blocked BDNF-induced NR1 phosphorylation. In animals with colitis, treatment with LY294002 (50 μg/kg, i.v.) blocked the Akt activity as well as NR1 phosphorylation at Ser896 in the spinal cord. Conclusion BDNF participates in colitis-induced spinal central sensitization by up-regulating NR1 phosphorylation at Ser896. The PI3K/Akt pathway, in addition to PLCγ and PKC, mediates BDNF action in the spinal cord during colitis
Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCγ, PKC, and PI3K/Akt pathways during colitis
Su1310 – Beta 2 Adrenergic Receptor Mediates the Activity of Satellite Glial Cells to Enhance Neuroinflammation, Colonic Damage, and Visceral Hypersensitivity
570 Norepinephrine Acts on β2-Adrenergic Receptor and Induces Glial Activation in Dorsal Root Ganglia via PKA and CA2+/CaMKII Pathways
Mo1873 Catecholaminergic Innervation Regulates Calcium Mobilization and CREB Activation in DRG Neuronal and Glial Cells
Tu1870 Up-Regulation of CREB Phosphorylation and CGRP Expression in Dorsal Root Ganglia by BDNF During Colitis
Tu1869 Molecular Basis of BDNF-Mediated Visceral Hypersensitivity in Colitis Involves Increased Responsiveness of Both DRG Neurons and Glial Cells to BDNF and BDNF-Induced Up-Regulation of Nociceptin and Prodynorphin
Tu1875 BDNF Regulates NMDA Receptor Phosphorylation via the PLC/PKC Pathway in the Spinal Cord During Colitis
Mo2034 Differential Expression of Phospho-AKT in Specifically Labeled Colonic Afferent Neurons Versus Bladder Afferent Neurons During Colitis
Additional file 1: of Endogenous BDNF augments NMDA receptor phosphorylation in the spinal cord via PLCÃŽÅ‚, PKC, and PI3K/Akt pathways during colitis
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