Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons

Background Cystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated. Results In a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter calcitonin gene-related peptide (CGRP) are increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. Cystitis-induced CGRP expression in L6 DRG is triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reverses CGRP up-regulation during cystitis. CGRP expression in the L6 DRG neurons is also enhanced by retrograde NGF signaling when NGF is applied to the nerve terminals of the ganglion-nerve two-compartmented preparation. Characterization of the signaling pathways in cystitis- or NGF-induced CGRP expression reveals that the activation (phosphorylation) of extracellular signal-regulated protein kinase (ERK)5 but not Akt is involved. In L6 DRG during cystitis, CGRP is co-localized with phospho-ERK5 but not phospho-Akt. NGF-evoked CGRP up-regulation is also blocked by inhibition of the MEK/ERK pathway with specific MEK inhibitors U0126 and PD98059, but not by inhibition of the PI3K/Akt pathway with inhibitor LY294002. Further examination shows that cystitis-induced cAMP-responsive element binding protein (CREB) activity is expressed in CGRP bladder afferent neurons and is co-localized with phospho-ERK5 but not phospho-Akt. Blockade of NGF action in vivo reduces the number of DRG neurons co-expressing CGRP and phospho-CREB, and reverses cystitis-induced increases in micturition frequency. Conclusions A specific pathway involving NGF-ERK5-CREB axis plays an essential role in cystitis-induced sensory activation

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

μ-4,4′-Bipyridine-bis­[aqua­(4-hy­droxy­pyridine-2,6-dicarboxyl­ato)copper(II)]

The title compound, [Cu2(C7H3NO5)2(C10H8N2)(H2O)2], exhibits a centrosymmetric binuclear molecule. Each completely deprotonated 4-hy­droxy­pyridine-2,6-dicarb­oxy­lic acid mol­ecule assumes a tridentate chelating coordination mode. The square-pyramidal coordination geometry around the CuII ion is completed by the bridging bipyridine ligand and an apical water molecule. Adjacent complexes are connected via O—H⋯O and C—H⋯O hydrogen bonds to generate a three-dimensional supra­molecular structure

Erbium-ytterbium co-doped lithium niobate single-mode microdisk laser with an ultralow threshold of 1 uW

We demonstrate single-mode microdisk lasers in the telecom band with ultra-low thresholds on erbium-ytterbium co-doped thin-film lithium niobate (TFLN). The active microdisk were fabricated with high-Q factors by photo-lithography assisted chemo-mechanical etching. Thanks to the erbium-ytterbium co-doping providing high optical gain, the ultra-low loss nanostructuring, and the excitation of high-Q coherent polygon modes which suppresses multi-mode lasing and allows high spatial mode overlap factor between pump and lasing modes, single-mode laser emission operating at 1530 nm wavelength was observed with an ultra-low threshold, under 980-nm-band optical pump. The threshold was measured as low as 1 uW, which is one order of magnitude smaller than the best results previously reported in single-mode active TFLN microlasers. And the conversion efficiency reaches 0.406%, which is also the highest value reported in single-mode active TFLN microlasers.Comment: 5 pages,3 figure

catena-Poly[[[aqua­(pyrazino[2,3-f][1,10]phenanthroline)cadium(II)]-μ-4,4′-ethyl­enedibenzoato] N,N-dimethyl­formamide hemisolvate]

In the title compound, [Cd(C16H10O4)(C14H8N4)(H2O)]·0.5C3H7NO, the CdII atom is six-coordinated by two N atoms from one pyrazino[2,3-f][1,10]phenanthroline ligand, three carboxyl­ate O atoms from two different 4,4′-ethyl­enedibenzoate ligands, and one water mol­ecule in a distorted octa­hedral environment. The two 4,4′-ethyl­enedibenzoate dianions are located on inversion centres bridging two neighboring CdII centres. O—H⋯O hydrogen-bonding inter­actions further stabilize the crystal structure. The DMF molecule is equally disordered about a center of inversion

Impulsive rotational Raman scattering of N2 by a remote "air laser" in femtosecond laser filament

We report on experimental realization of impulsive rotational Raman scattering from neutral nitrogen molecules in a femtosecond laser filament using an intense self-induced white-light seeding "air laser" generated during the filamentation of an 800 nm Ti: Sapphire laser in nitrogen gas. The impulsive rotational Raman fingerprint signals are observed with a maximum conversion efficiency of ~0.8%. Our observation provides a promising way of remote identification and location of chemical species in atmosphere by rotational Raman scattering of molecules.Comment: 4 pages, 4 figure