NMDA receptors (NMDARs) modulate glutamatergic excitatory tone in the brain via two complementary modalities: a phasic excitatory postsynaptic current and a tonic extrasynaptic modality. Here, we demonstrated that the tonic NMDAR-current ( ) mediated by NR2A-containing NMDARs is an efficient biosensor detecting the altered ambient glutamate level in the supraoptic nucleus (SON). of magnocellular neurosecretory cells (MNCs) measured by nonselective NMDARs antagonist, AP5, at holding potential ( ) -70 mV in low concentration of ECF Mg ([Mg]) was transiently but significantly increased 1-week post induction of a DOCA salt hypertensive model rat which was compatible with that induced by a NR2A-selective antagonist, PEAQX ( ) in both DOCA-HO and DOCA-salt groups.
View Article and Find Full Text PDFNR2D subunit-containing NMDA receptors (NMDARs) gradually disappear during brain maturation but can be recruited by pathophysiological stimuli in the adult brain. Here, we report that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication recruited NR2D subunit-containing NMDARs that generated an Mg-resistant tonic NMDA current (I) in dopaminergic (DA) neurons in the midbrain of mature male mice. MPTP selectively generated an Mg-resistant tonic I in DA neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA).
View Article and Find Full Text PDFMAO-B inhibitors have been implicated to reverse neuropathic pain behaviors. Our previous study has demonstrated that KDS2010 (KDS), a newly developed reversible MAO-B inhibitor, could attenuate Paclitaxel (PTX)-induced tactile hypersensitivity in mice through suppressing reactive oxidant species (ROS)-decreased inhibitory GABA synaptic transmission in the spinal cord. In this study, we evaluated the analgesic effect of KDS under a new approach, in which KDS acts on dorsal horn sensory neurons to reduce excitatory transmission.
View Article and Find Full Text PDFTargeting microglial activation is emerging as a clinically promising drug target for neuropathic pain treatment. Fexofenadine, a histamine receptor 1 antagonist, is a clinical drug for the management of allergic reactions as well as pain and inflammation. However, the effect of fexofenadine on microglial activation and pain behaviors remains elucidated.
View Article and Find Full Text PDFMonoamine oxidase (MAO) inhibitors have been investigated for the treatment of neuropathic pain. Here, we assessed the antiallodynic effects of a novel MAO-B inhibitor, KDS2010, on paclitaxel (PTX)-induced mechanical hypersensitivity. Oral administration of KDS2010 effectively relieved PTX-induced mechanical hypersensitivity in a dose-dependent manner.
View Article and Find Full Text PDFNanomedicine (Lond)
August 2020
Neuropathic pain is one of the most intense types of chronic pain; it constitutes a pervasive complaint throughout the public health system. With few effective treatments, it remains a significant challenge. Commercially available drugs for neuropathic pain are still limited and have disappointing efficacy.
View Article and Find Full Text PDFWe investigated whether miRNA (miR) 146a-5p-loaded nanoparticles (NPs) can attenuate neuropathic pain behaviors in the rat spinal nerve ligation-induced neuropathic pain model by inhibiting activation of the NF-κB and p38 MAPK pathways in spinal microglia. After NP preparation, miR NPs were assessed for their physical characteristics and then injected intrathecally into the spinal cords of rat spinal nerve ligation rats to test their analgesic effects. miR NPs reduced pain behaviors for 11 days by negatively regulating the inflammatory response in spinal microglia.
View Article and Find Full Text PDFInt J Environ Res Public Health
January 2020
As purchase power and consumption knowledge increase, consumers gradually demand safer and healthier products. In addition, consumers focus greater attention on organic food. This study investigates the relationship between environmental consciousness and organic food purchase intention with the mediating roles of perceived food quality and price sensitivity.
View Article and Find Full Text PDFMicroglia, the resident macrophages, act as the first and main form of active immune defense in the central nervous system. Arginase 2 (Arg2) is an enzyme involved in L-arginine metabolism and is expressed in macrophages and nervous tissue. In this study, we determined whether the absence of Arg2 plays a beneficial or detrimental role in the neuroinflammatory process.
View Article and Find Full Text PDFUpon peripheral nerve injury, vesicular ATP is released from damaged primary afferent neurons. This extracellular ATP subsequently activates purinergic receptors of the spinal cord, which play a critical role in neuropathic pain. As an inhibitor of the vesicular nucleotide transporter (VNUT), Evans blue (EB) inhibits the vesicular storage and release of ATP in neurons.
View Article and Find Full Text PDFActive nanoscale powders of cubic phase zirconia stabilized with yttria, gadolinia, and scandia were successfully prepared by urea hydrolysis. Synthetic cubic zirconia powders had homogeneous, nanoscale, and less-agglomeration characteristics. Dense pellets of grain size about 0.
View Article and Find Full Text PDFYeast cells transformed with high-copy number plasmids comprising a green fluorescent protein (GFP)-encoding gene optimized for yeast under the control of the new DIN7 or PLM2 and the established RNR2 and RAD54 promoters were used to assess the genotoxic potential of chemical compounds. The activity of potential DNA-damaging agents was investigated by genotoxicity assays and by OxoPlate assay in the presence of various test compounds. The fluorescence signal generated by GFP in response to DNA damage was related to the different concentrations of analytes and the analyte-dependent GFP synthesis.
View Article and Find Full Text PDFAntiretroviral therapy (ART) retention and 5 early-warning indicators (EWIs) of HIV drug resistance (HIVDR) were abstracted at 27 adult and 4 pediatric clinics in Vietnam in 2009. Of 4531 adults and 313 children, 81.2% and 84.
View Article and Find Full Text PDFPurpose: The purpose of this paper is to examine the relative efficiency and productivity of hospitals during the health reform process.
Design/methodology/approach: Data envelopment analyses method (DEA) with the input-oriented variable-returns-to-scale model was used to calculate efficiency scores. Malmquist total factor productivity index approach was then employed to calculate productivity of hospitals.
CdS/CdSe/CdS quantum-dot quantum-well heterostructures with the different thicknesses of CdSe well layers were synthesized by using the colloidal chemical method. The absorption, photoluminescence and Raman scattering spectra of CdS cores, and CdS/CdSe, CdS/CdSe/CdS structures were investigated. A comparative study of their optical properties confirmed the formation of CdSe well and exterior CdS shell.
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