ABSTRACT
High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC; mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1µM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gßγ blocker (gallein, 100µM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5µg/mL) and cholera toxin (CTX) (0.5µg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.
Subject(s)
Calcium Channels/metabolism , Ganglia, Spinal/physiology , Neurons/physiology , Receptors, G-Protein-Coupled/metabolism , Type C Phospholipases/metabolism , Animals , Cells, Cultured , Disease Models, Animal , Ganglia, Spinal/drug effects , Ganglia, Spinal/physiopathology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Hyperalgesia/drug therapy , Hyperalgesia/physiopathology , Male , Mice, Knockout , Mice, Transgenic , Neurons/drug effects , Patch-Clamp Techniques , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled/agonists , Spinal Nerves/injuries , Type C Phospholipases/antagonists & inhibitorsABSTRACT
PURPOSE: This study was performed to investigate the association between the mid-brain serotonin transporter (SERT) availability and intelligence quotient (IQ). METHODS: One hundred and thirteen healthy participants, including 52 male and 61 female subjects, were recruited. We used SPECT with [(123)I]ADAM images to determine the SERT availability in the mid-brain, and measured the subjects' IQ using the WAIS-R. RESULTS: We found a significant positive correlation between the mid-brain SERT availability and the IQ of the participants. Even when controlling for age and sex, the significant association still existed. CONCLUSION: This result implied that the higher the SERT binding in the mid-brain, the better the IQ in healthy participants.
Subject(s)
Brain/metabolism , Intelligence , Serotonin Plasma Membrane Transport Proteins/metabolism , Adult , Female , Healthy Volunteers , Humans , Iodine Radioisotopes , Male , Neuroimaging/methods , Tomography, Emission-Computed, Single-Photon/methodsABSTRACT
Our experimental results demonstrate that full-field hard-X-ray microscopy is finally able to investigate the internal structure of cells in tissues. This result was made possible by three main factors: the use of a coherent (synchrotron) source of X-rays, the exploitation of contrast mechanisms based on the real part of the refractive index and the magnification provided by high-resolution Fresnel zone-plate objectives. We specifically obtained high-quality microradiographs of human and mouse cells with 29 nm Rayleigh spatial resolution and verified that tomographic reconstruction could be implemented with a final resolution level suitable for subcellular features. We also demonstrated that a phase retrieval method based on a wave propagation algorithm could yield good subcellular images starting from a series of defocused microradiographs. The concluding discussion compares cellular and subcellular hard-X-ray microradiology with other techniques and evaluates its potential impact on biomedical research.
Subject(s)
Cellular Structures/cytology , Image Processing, Computer-Assisted/methods , Microradiography/methods , Microscopy/methods , Algorithms , Animals , Aorta/cytology , Equipment Design , Gold , HeLa Cells , Humans , Metal Nanoparticles/analysis , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microradiography/instrumentation , Microscopy/instrumentation , Neoplasms, Experimental/pathology , Synchrotrons , Tomography, X-Ray Computed/methods , X-Rays , ZebrafishABSTRACT
A 65-year-old woman presented with mild dysphagia, weight loss and intermittent palpitation. Chest radiograph revealed a large opacity in the right lower lung field. Subsequent CT scan showed a large posterior mediastinal lipoma extending from the level of the aortic arch to the thoracoabdominal junction. After thoracoscopic resection, the patient's dysphagia and palpitation were resolved. After a follow-up of 2 years, the patient has had no evidence of recurrence.
