A5022425643- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Attention Deficit Hyperactivity Disorder
- Autism Spectrum Disorder Research
- Tryptophan and brain disorders
- Genetics, Aging, and Longevity in Model Organisms
- Bipolar Disorder and Treatment
- Amino Acid Enzymes and Metabolism
- Memory and Neural Mechanisms
- Genetics and Neurodevelopmental Disorders
- Neuroendocrine regulation and behavior
- Quantum Dots Synthesis And Properties
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Stress Responses and Cortisol
- Cellular transport and secretion
- Circadian rhythm and melatonin
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Treatment of Major Depression
- Cholinesterase and Neurodegenerative Diseases
Florida Atlantic University
2016-2024
Jupiter Medical Center
2016-2024
Allen Institute for Brain Science
2012-2024
Italian Institute of Technology
2023
Weatherford College
2023
Medical University of Vienna
2023
Silva
2023
University of Copenhagen
2023
TU Wien
2023
University of Pittsburgh
2004-2021
A Na(+)- and Cl(-)-coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, pulmonary membranes. The brain 5HT appears to be a principal site of action therapeutic antidepressants may mediate behavioral and/or toxic effects cocaine amphetamines. Oligonucleotides derived from consensus sequences were used identify placental cDNAs highly related the rat carrier. Transfection one these into HeLa cells yields high-affinity (Km = 463 nM),...
Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope associated with postural tachycardia plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis impaired functioning of transporter contributes pathophysiologic mechanism orthostatic intolerance.
Parkinson's disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, neuronal degeneration can be triggered through exposure to neurotoxins accumulated presynaptic transporter (DAT), including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium. We have established system for pharmacological genetic evaluation neurotoxin-induced in Caenorhabditis elegans . Brief (1 h) green fluorescent protein-tagged, living worms 6-OHDA causes...
Many psychotropic drugs interfere with the reuptake of dopamine, norepinephrine, and serotonin. Transport capacity is regulated by kinase-linked pathways, particularly those involving protein kinase C (PKC), resulting in transporter phosphorylation sequestration. Phosphorylation sequestration serotonin (SERT) were substantially impacted ligand occupancy. Ligands that can permeate transporter, such as or amphetamines, prevented PKC-dependent SERT phosphorylation. Nontransported antagonists...
Antidepressant- and cocaine-sensitive serotonin (5-hydroxytryptamine, 5-HT) transporters (SERTs) dictate clearance of extracellular 5-HT after release. To explore protein kinase C-mediated SERT regulation, we generated a stable human (hSERT)-expressing cell line (293-hSERT) evaluated modulation activity via studies flux, hSERT-mediated currents under voltage clamp, surface distribution protein. 293-hSERT cells exhibit saturable, high-affinity, antidepressant-sensitive uptake as well...
Overexpression of human alpha-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical pathological changes that mimic synucleopathies Parkinson's disease. We have overexpressed both wild-type (WT) mutant alanine53-->threonine (A53T) by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T was with a pan-neuronal motor neuron promoter. Neuronal dendritic loss accelerated all three sets C. elegans...
Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The transporter (SERT) gene ( SLC6A4 ) has been associated with whole blood levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children ASD. Here establish that transgenic mice expressing the most common of these variants, Ala56, exhibit elevated, p38 MAPK-dependent phosphorylation,...
To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored ability serotonin-labeled CdSe (SNACs) interact with antidepressant-sensitive, human Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found dose-dependently inhibit transport radiolabeled by hSERT dSERT, an estimated half-maximal activity (EC50) 33 (dSERT) 99 μM (hSERT)....
Antidepressant-sensitive serotonin (5-hydroxytrypta-mine, 5HT) transporters (SERTs) are responsible for efficient synaptic clearance of extracellular 5HT. Previously (Qian, Y., Galli, A., Ramamoorthy, S., Risso, DeFelice, L. J., and Blakely, R. D. (1997) J. Neurosci. 17, 45–47), we demonstrated that protein kinase (PKC)-linked pathways in transfected HEK-293 cells lead to the internalization cell-surface human (h) SERT a reduction 5HT uptake capacity. In present study, report PKC activators...
High performance liquid chromatography studies documented the presence of an enzyme activity, N-acetylated alpha-linked acidic dipeptidase (NAALA dipeptidase), in rat brain membranes that cleaves endogenous dipeptide, N-acetyl-L-aspartyl-L-glutamate to N-acetyl-aspartate and glutamate. With ion exchange chromatography, which quantitatively separated [3,4-3H]glutamate from N-acetyl-L-aspartyl-L-[3,4-3H]glutamate, we found NAALA activity was essentially restricted nervous tissue kidney. We...
Drugs of abuse, including cocaine, amphetamine (AMPH), and heroin, elevate extracellular dopamine (DA) levels in the brain, thereby altering activity/plasticity reward circuits precipitating addiction. The physiological release DA occurs through calcium-dependent fusion a synaptic vesicle with plasma membrane. Extracellular is cleared by uptake Na + /Cl - -dependent transporter (DAT). In contrast, substrate AMPH induces nonvesicular mediated DAT. generally believed to trigger efflux DAT...
Norepinephrine (NE) transporters (NETs) constitute the primary mechanism for inactivation of synaptically released NE, are targets multiple antidepressants and psychostimulants, have been reported to be deficient in affective autonomic disorders. Although regional distribution NETs has defined through synaptosomal transport autoradiographic approaches, NET protein expression yet characterized fully central nervous system (CNS). We identified a cytoplasmic epitope (amino acids 585-602)...
Nonspecific binding is a frequently encountered problem with fluorescent labeling of tissue cultures when labeled quantum dots. In these studies various cell lines were examined for nonspecific binding. Evidence suggests that related to type and may be significantly reduced by functionalizing dots poly(ethylene glycol) ligands (PEG). The length PEG required give significant reduction in as short 12−14 ethylene glycol units.