A5022467023- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Gastrointestinal motility and disorders
- Nerve injury and regeneration
- Neuroscience and Neural Engineering
- Ion channel regulation and function
- Alzheimer's disease research and treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Retinal Development and Disorders
- Gastroesophageal reflux and treatments
- Congenital gastrointestinal and neural anomalies
- Neurogenesis and neuroplasticity mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Signaling Pathways in Disease
- GABA and Rice Research
- Nicotinic Acetylcholine Receptors Study
- Muscle Physiology and Disorders
- Cardiac Arrhythmias and Treatments
- Cardiomyopathy and Myosin Studies
- Phosphodiesterase function and regulation
- Eosinophilic Esophagitis
- Trypanosoma species research and implications
- Intestinal Malrotation and Obstruction Disorders
- Ubiquitin and proteasome pathways
- Memory and Neural Mechanisms
Daiichi Sankyo (United States)
2023
Synergy Pharmaceuticals (United States)
2018-2021
Rutgers, The State University of New Jersey
1998-2015
Pfizer (United States)
2010
Princeton University
2007-2008
Massachusetts Institute of Technology
2003-2007
Howard Hughes Medical Institute
2003-2007
Neurotrophins (NTs) have recently been found to regulate synaptic transmission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced strength. Specifically, brain-derived neurotrophic factor augmented glutamate-evoked, but not acetylcholine-evoked, currents 3-fold increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate were affected by...
Long-term depression (LTD) induced by low-frequency synaptic stimulation (LFS) was originally introduced as a model to probe potential mechanisms of deprivation-induced in visual cortex. In hippocampus, LTD requires activation postsynaptic NMDA receptors, PKA, and the clathrin-dependent endocytosis α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. It has long been assumed that cortical layer 2/3 LFS 4 uses similar mechanisms. Here we show mouse cortex this conclusion...
OBJECTIVES: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome constipation (IBS-C). METHODS: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or (3 6 mg) 12 weeks. The primary end point was percentage overall responders (patients reporting ≥30% reduction from baseline worst abdominal pain plus an increase ≥1 complete spontaneous movement...
Expression of N-methyl d-aspartate (NMDA) receptor-dependent homosynaptic long term depression at synapses in the hippocampus and neocortex requires persistent dephosphorylation postsynaptic protein kinase A substrates. An attractive mechanism for expression is loss surface AMPA (alpha-amino-3-hydroxy-5-methylisoxazale-4-propionate) receptors synapses. Here we show that a threshold level NMDA receptor activation must be exceeded to trigger stable from cultured hippocampal neurons. also...
Rapamycin is an immunosuppressive immunophilin ligand reported as having neurotrophic activity. We show that modification of rapamycin at the mammalian target (mTOR) binding region yields ligands, WYE-592 and ILS-920, with potent activities in cortical neuronal cultures, efficacy a rodent model for ischemic stroke, significantly reduced Surprisingly, both compounds showed higher selectivity FKBP52 versus FKBP12, contrast to previously ligands. Affinity purification revealed two key proteins,...
The recently identified Mas-related gene (Mrg) family of G-protein-coupled receptors is expressed almost exclusively in dorsal root ganglion (DRG) neurons. expression one member, MrgD, even further confined to IB4+, nonpeptidergic, small-diameter nociceptors. Although the functional consequences MrgD activation are not known, this profile provides intriguing potential for a role pain sensation or modulation. In recombinant cell line, we first assessed significance by coexpressing with...
Application of brain-derived neurotrophic factor (BDNF) to hippocampal neurons has profound effects on glutamatergic synaptic transmission. Both pre- and postsynaptic actions have been identified that depend the age type preparation. To understand nature this diversity, we begun examine mechanisms BDNF action in cultured dissociated embryonic neurons. Whole-cell patch-clamp recording during iontophoretic application glutamate revealed doubled amplitude induced inward current. Coexposure NMDA...
Brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic transmission, is known to influence associative plasticity and refinement neural connectivity. We now show that BDNF modulation glutamate currents in hippocampal neurons exhibits the additional property use dependence, postsynaptic mechanism resulting selective active channels. demonstrate selectivity by varying repetition rate iontophoretically applied pulses during exposure. During relatively high-frequency (0.1 Hz),...
Brain-derived neurotrophic factor (BDNF) modulates synaptic strength in hippocampal neurons, addition to promoting survival and differentiation. To identify genes involved trophic regulation of plasticity, we have used a multidisciplinary approach differential display family-specific slot blots combination with whole-cell patch-clamp recordings dissociated neurons. Three hour exposure BDNF elicited 2.6-fold increase charge concomitant induction 11 as revealed by display, including the small...
Trophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence these mechanisms their temporal relationships are undefined. vesicle protein Rab3A is required for the early, initial 10 min phase but not later BDNF-enhanced transmission. We now examine distinction mechanistic between phases BDNF action. mutant cells did exhibit increased miniature EPSC frequency in response to cell culture, indicating an absence component. In...
The BURDEN IBS-C study was conducted to better understand the experiences, attitudes, and unmet needs of sufferers irritable bowel syndrome with constipation (IBS-C) in comparison perceptions challenges healthcare providers (HCPs) who treat patients. This an author-developed, online questionnaire using KnowledgePanel® survey individuals (N = 1311). HCPs participated a complementary were recruited separately 331). fielded from June 29, 2016, January 30, 2017. Most patients had used (86%)...
Type I spiral ganglion neurons have a unique role relative to other sensory afferents because, as single population, they must convey the richness, complexity, and precision of auditory information shape signals transmitted brain. To understand better sophistication response properties, we compared somatic whole-cell current-clamp recordings from basal apical obtained during first 2 postnatal weeks CBA/CaJ mice. We found that this developmental time period neuron properties changed uniformly...
Non-recommended dosing occurs in ~25-50% of non-vitamin K antagonist oral anticoagulant prescriptions, with limited data for edoxaban. We analyzed edoxaban patterns atrial fibrillation patients from the Global ETNA-AF program, relating to baseline characteristics and 1-year clinical outcomes. The following groups were compared: non-recommended 60 mg ("overdosed") vs. recommended 30 mg; ("underdosed") mg. Most (22,166/26,823; 82.6%) received doses. was more frequent near label-specified...
Objective: This open-label, multi-center, fixed-dose study (NCT02706483) evaluated the long-term safety and tolerability of plecanatide for treatment adults with irritable bowel syndrome constipation (IBS-C).Methods: Safety once-daily 6 mg up to 53 weeks was assessed in patients IBS-C who either had been enrolled one phase 3 studies or were study-naïve but met eligibility criteria double-blind studies. by treatment-emergent adverse events (AEs). Patient-reported questionnaires overall IBS...
Diverse action potential shapes and kinetics resulting from dynamic heterogeneity in spiral ganglion neurons are axonally transmitted as multiplexed signals that retain the fine structure of each distinctive waveform within a digital code.
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen indicated for patients with gene amenable to exon 53 skipping. Here, we report safety, function, first results from open-label, phase II Galactic53 trial of viltolarsen (NCT04956289). Male participants aged ≥ 8 years DMD received 80 mg/kg intravenous once weekly 48 weeks. Results receiving were compared external...
Two hallmarks of Alzheimer's Disease (AD) are the accumulation senile plaques containing insoluble amyloid beta and neurofibrillary tangles arising from aggregation hyperphosphorylated tau. Tau, found in axons, binds to stabilizes microtubules which, turn, provide structural support a scaffold for shuttling essential proteins between cell body axon. Microtubule function is governed by dynamic equilibrium phosphorylation dephosphorylation mechanisms; however, aberrant hyperphosphorylation tau...
Introduction: Constipation, including Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with (IBS-C), is prevalent in patients aged 65 older. Currently, there limited clinical trial safety/tolerability data older adults. Recently, two CIC IBS-C trials plecanatide were completed which represent the largest Phase 3 to date each of these disorders. All permitted enrollment eligible up age 80 85, respectively. Rome IV supports concept as a spectrum disorders overlapping...