A5017733630- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Circadian rhythm and melatonin
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Ion channel regulation and function
- Memory and Neural Mechanisms
- Retinal Development and Disorders
- Molecular Sensors and Ion Detection
- Traumatic Brain Injury and Neurovascular Disturbances
- Neurotransmitter Receptor Influence on Behavior
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Traumatic Ocular and Foreign Body Injuries
- Neural dynamics and brain function
- Glaucoma and retinal disorders
- S100 Proteins and Annexins
- Pharmacological Receptor Mechanisms and Effects
- Nicotinic Acetylcholine Receptors Study
- Connexins and lens biology
- Intracerebral and Subarachnoid Hemorrhage Research
- Acute Ischemic Stroke Management
- Neonatal and fetal brain pathology
The University of Texas at Austin
2021-2025
Emory University
2004-2021
NeurOp (United States)
2014
Georgia Institute of Technology
2008
Duke University
2008
Université de Caen Normandie
2005
Centre National de la Recherche Scientifique
2005
University of Arkansas for Medical Sciences
2003
State University of New York
2003
National University of Singapore
2003
Zinc inhibits NMDA receptor function through both voltage-dependent and voltage-independent mechanisms. In this report we have investigated the role that NR1 subunit plays in Zn2+ inhibition. Our data show inclusion of exon 5 into increases IC50 for inhibition from 3-fold to 10-fold when full length 22 is also spliced mature transcript complex contains NR2A or NR2B subunits; has little effect on receptors contain NR2C NR2D. Mutagenesis within indicates same residues control proton...
Although serine proteases and their receptors are best known for role in blood coagulation fibrinolysis, the CNS expresses many components of an extracellular protease signaling system including protease-activated receptor-1 (PAR1), which thrombin is most effective activator. In this report we show that activation PAR1 potentiates hippocampal NMDA receptor responses CA1 pyramidal cells by 2.07 +/- 0.27-fold (mean SEM). Potentiation neuronal can be blocked a protein kinase inhibitor, effects...
We have compared the potencies of structurally distinct channel blockers at recombinant NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptors. The IC 50 values varied with stereochemistry subunit composition, suggesting that it may be possible to design subunit‐selective blockers. For dizocilpine (MK‐801), differential potency MK‐801 stereoisomers determined NMDA receptors was confirmed native in vitro vivo . Since proton sensor is tightly linked both functionally gating, we examined whether...
The four <i>N</i>-methyl-d-aspartate (NMDA) receptor NR2 subunits (NR2A-D) have different developmental, anatomical, and functional profiles that allow them to serve roles in normal neuropathological situations. Identification of subunit-selective NMDA agonists, antagonists, or modulators could prove be both valuable pharmacological tools as well potential new therapeutic agents. We evaluated the potency efficacy a wide range glutamate-like compounds at NR1/NR2A, NR1/NR2B, NR1/NR2C, NR1/NR2D...
Modulation of the N- methyl- d -aspartate (NMDA)-selective glutamate receptors by extracellular protons and Zn 2+ may play important roles during ischemia in brain seizures. Recombinant NR1/NR2A exhibit a much higher apparent affinity for voltage-independent inhibition than with other subunit combinations. Here, we show that mechanism this high-affinity, NR2A-containing results from enhancement proton inhibition. We also N-terminal leucine/isoleucine/valine binding protein (LIVBP)-like...
We have studied the involvement of thrombin receptor [protease-activated receptor-1 (PAR-1)] in astrogliosis, because extravasation PAR-1 activators, such as thrombin, into brain parenchyma can occur after blood-brain barrier breakdown a number CNS disorders. PAR1 - / animals show reduced astrocytic response to cortical stab wound, suggesting that activation plays key role astrogliosis associated with glial scar formation injury. This interpretation is supported by finding selective vivo...
Significance Circadian rhythms are not simply a passive consequence of cyclic fluctuations in the environment, but instead originate within organism. Accumulating evidence indicates that disruption circadian contributes to development many diseases. Here, we demonstrate removal clock gene Bmal1 from retina has multiple effects on rod and cone pathways. In pathway, primary effect is viability, an accentuated aging mice. observed retinal caused stunting bipolar cell dendrites thinning outer...
Extracellular protons inhibit <i>N</i>-methyl-d-aspartate (NMDA) receptors with an IC<sub>50</sub> value in the physiological pH range. To identify molecular determinants of proton sensitivity, we used scanning mutagenesis NR1 subunit to search for residues that control inhibition NMDA receptors. Homology modeling extracellular domains suggested at which mutations perturbed sensitivity were localized discrete regions. The majority strongly affected clustered end second transmembrane domain...
At the heart of prefrontal network is mediodorsal (MD) thalamus. Despite importance MD in a broad range behaviors and neuropsychiatric disorders, little known about physiology neurons MD. We injected retrograde tracer cholera toxin subunit B (CTB) into medial cortex (mPFC) adult wild-type mice. prepared acute brain slices used current clamp electrophysiology to measure compare intrinsic properties that project mPFC (MD→mPFC neurons). show MD→mPFC are located predominantly (MD-M) lateral...
Abstract Background The neurodevelopmental disorder Fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene which prevents FMRP production. modulates expression and function a wide variety proteins, including voltage-gated ion channels such as Hyperpolarization-Activated Cyclic Nucleotide gated (HCN) channels, are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving mediodorsal thalamus (MD), has been implicated disorders. MD...
Cardiovascular and neurologic surgeries often involve a temporary reduction in cerebral blood flow. In these conditions, as well during ischemia traumatic brain injury, the loss of oxygen glucose initiates cascade cellular events that culminate neuronal death damage. Understanding mechanisms contribute to after hypoxia/ischemia is critically important for treatment such injury. Here, we use model combined (H/I) examine role protease-activated receptor-1 (PAR-1) hypoxic/ischemic Our data show...
A wealth of genetic information is available describing single-nucleotide variants in the human population that appear to be well-tolerated and themselves do not confer disease. These variant data sets contain signatures about protein structure-function relationships provide an unbiased view various functions context health. This can used determine regional intolerance variation, defined as missense tolerance ratio (MTR), which indicator stretches polypeptide chain tolerate changes without...
Ocular blast injury is a major medical concern for soldiers and explosion victims due to poor visual outcomes. To define the changes in gene expression following eye, we examined retinal ribonucleic acid (RNA) 54 mouse strains 5 days after single 50-psi overpressure air wave injury. We observe that almost 40% of genes are differentially expressed with false discovery rate (FDR) <0.001, even though nominal RNA rather small. Moreover, find through machine learning approaches genetic networks...
Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. compounds potent and selective inhibitors NR2B-containing recombinant receptors IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity...
We describe a clinical candidate molecule from new series of glutamate N -methyl-d-aspartate receptor subunit 2B–selective inhibitors that shows enhanced inhibition at extracellular acidic pH values relative to physiologic pH. This property should render these compounds more effective receptors synapses responding high frequency action potentials, since glutamate-containing vesicles are within their lumen. In addition, acidification penumbral regions around ischemic tissue also enhance...
Purpose: The present study tested the hypothesis that connexin-36 (Cx36) and gap junctions between photoreceptor cells contribute to circadian rhythm of photopic electroretinogram (ERG) b-wave amplitude. Methods: Cone-specific disruption Cx36 was obtained in mice with a floxed Gjd2 gene human red/green pigment promoter (HRGP)-driven Cre recombinase. Standard ERG, spectral-domain optical coherence tomography (SD-OCT) histochemical methods were used. Results: HRGPcreGjd2fl/fl had selective...