ABSTRACT
Noxious mechanical information is transmitted through molecularly distinct nociceptors, with pinprick-evoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2 (Npy2r) and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD. However, the molecular programs controlling their development are only beginning to be understood. Here we demonstrate that Npy2r-expressing sensory neurons are in fact divided into two groups, based on transient or persistent Npy2r expression. Npy2r-transient neurons are myelinated, likely including A-fiber nociceptors, whereas Npy2r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb. We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2r-transient A-fiber nociceptors and MrgprD C-fiber nociceptors, respectively. Behaviorally, mice with conditional knockout of Nfia, but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses. Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.
ABSTRACT
The neuronal activity-dependent change in the manner in which light is absorbed or scattered in brain tissue is called the intrinsic optical signal (IOS), and provides label-free, minimally invasive, and high spatial (~100 µm) resolution imaging for visualizing neuronal activity patterns. IOS imaging in isolated brain slices measured at an infrared wavelength (>700 nm) has recently been attributed to the changes in light scattering and transmittance due to aquaporin-4 (AQP4)-dependent astrocytic swelling. The complexity of functional interactions between neurons and astrocytes, however, has prevented the elucidation of the series of molecular mechanisms leading to the generation of IOS. Here, we pharmacologically dissected the IOS in the acutely prepared brain slices of the stratum radiatum of the hippocampus, induced by 1 s/20 Hz electrical stimulation of Schaffer-collateral pathway with simultaneous measurement of the activity of the neuronal population by field potential recordings. We found that 55% of IOSs peak upon stimulation and originate from postsynaptic AMPA and NMDA receptors. The remaining originated from presynaptic action potentials and vesicle fusion. Mechanistically, the elevated extracellular glutamate and K⁺ during synaptic transmission were taken up by astrocytes via a glutamate transporter and quinine-sensitive K2P channel, followed by an influx of water via AQP-4. We also found that the decay of IOS is mediated by the DCPIB- and NPPB-sensitive anion channels in astrocytes. Altogether, our results demonstrate that the functional coupling between synaptic activity and astrocytic transient volume change during excitatory synaptic transmission is the major source of IOS.
Subject(s)
Action Potentials , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Amino Acid Transport System X-AG , Astrocytes , Brain , Electric Stimulation , Glutamic Acid , Hippocampus , Jupiter , Neurons , Receptors, N-Methyl-D-Aspartate , Synaptic Transmission , WaterABSTRACT
PURPOSE: To maintain the homeostasis of stem cells and prevent their ability to initiate tumorigenesis, it is important to identify and modify factors that prevent or accelerate stem cell senescence. We used microarrays to attempt to identify such factors in human amniotic fluid (HAF)-derived stem cells. MATERIALS AND METHODS: To identify gene expression changes over a time course, we compared gene expression profiles of HAF-derived stem cells in different passages (1st, 2nd, 4th, 6th, 8th, and 10th) using a Sentrix Human illumina microarray. RESULTS: Of the 25,804 genes in the microarray chip, 1,970 showed an over 2-fold change relative to the control (the 1st passage)-either upregulated or downregulated. Quantitative real-time PCR validated the microarray data for selected genes: markedly increased genes were CXCL12, cadherin 6 (CDH6), and folate receptor 3 (FOLR3). Downregulated genes included cyclin D2, keratin 8, insulin-like growth factor 2 (IGF2), natriuretic peptide precursor B (NPPB) and cellular retinoic acid binding protein 2 (CRABP2). The expression pattern of the selected genes was consistent with the microarray data except for CXCL12 and IGF2. Interestingly, the expression of NPPB was dramatically downregulated along the time course; it was almost completely shut-down by the 10th passage. In contrast, FOLR3 mRNA expression was dramatically increased. CONCLUSION: Taken together, although a function for NPPB and FOLR3 in stem cell senescence has not been reported, our results strongly suggest that NPPB and/or FOLR3 play a significant role in the regulation of stem cell senescence.
Subject(s)
Female , Humans , Aging , Amniotic Fluid , Carrier Proteins , Cell Transformation, Neoplastic , Cyclin D2 , Folic Acid , Gene Expression , Homeostasis , Keratin-8 , Nitrobenzoates , Real-Time Polymerase Chain Reaction , RNA, Messenger , Stem Cells , Transcriptome , TretinoinABSTRACT
@#Objective To observe the variation of cerebral brain flow (CBF)and pathological characteristics in peripheral brain tissue of nidus after operation of brain arterivenous malformations (BAVM) and explore the mechanism and theaputic strategy of normal perfusion pressure breakdown (NPPB)after microsurgery. Methods 12 cases of BAVM that have received surgical resection were analyzed prospectively, and 8 cases of them were embolized with Onyx. The pathological characteristics of the nidus and peripheral brain tissue was observed with microscope and electron microscope. The variation of CBF in peripheral brain tissue of the nidus following microsurgical resection was observed by using Laser Doppuler Perfusion Imaging (LDPI) system. The monitering result of CBF in little meniugioma(n=6) during surgery was used as the control. Results There was small vessel expantion, neuron necrosis, gliocyte hyperplasia and blood brain barriar (BBB) destruction in peripheral brain tissue of BAVM nidus, the visibal brain tissue edema and inflammatory cell infiltration in peripheral brain tissue of the nidus and the revascularization in the emolized nidus vessels were observed after embolization with Onyx. There was significant change of CBF between pre-and post-operation (P<0.05),and after controlling depressurization during surgery was the increasing CBF step down (P<0.05). Conclusion The BBB breakdown and increasing CBF of peripheral brain tissue of the nidus may be the pathological foundation of brain hemorrhage and edema after BAVM microsurgical resection. So embolization before the operation, controlling depressuriation during and after surgery is the important methods for preventing and curing the NPPB of BAVM after microsurgery.
ABSTRACT
Objectives:To examine the effect of chloride blocker (NPPB and tamoxifen)on volume sensitive chloride channels in mouse cardiac ventricular myocytes. Methods:Isolated mouse cardiac ventricular myocytes were subjected to whole cell patch clamp to record the hypotonicity activated chloride currents. Results:When the myocytes were exposed to hypotonic solution, an obvious whole cell currents were activated. The currents were inhibited by extracellular NPPB reversibly and significantly. The specific blocker for volume sensitive chloride channel , tamoxifen (50 ?mol/L), could apparently block the activity of this channel in a voltage dependent manner. Conclusions:Mouse cardiac ventricular myocytes process volume sensitive chloride channel which is sensitive to NPPB and tamoxifen.
ABSTRACT
To investigate the effects of preoperative intravascular embolization on treatment of intracranial giant arteriovenous malformations (AVMs), 27 patients with intracranial giant AVMs were successfully treated from August, 1997 to April 1998 every patient was treated with preoperative intravascular embolization. Compared with single surgical resection, it was found that surgical resection after intravenous embolization can greatly reduce the intraoperative hemorrhage, diminish postoperative mortality and morbidity, and prevent normal perfusion pressure breakthrough (NPPB) significantly. The present study suggested that combination of surgical resection and intravascular embolization was an effect way in the treatment of giant cerebral AVMs.