A5020782011- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Sleep and Wakefulness Research
- Photoreceptor and optogenetics research
- Neuroendocrine regulation and behavior
- melanin and skin pigmentation
- Circadian rhythm and melatonin
- Immune Cell Function and Interaction
- Receptor Mechanisms and Signaling
- Genomics, phytochemicals, and oxidative stress
- Neuroscience and Neural Engineering
- Neuropeptides and Animal Physiology
- Dietary Effects on Health
- Neurotransmitter Receptor Influence on Behavior
- Ion Channels and Receptors
- Pancreatic function and diabetes
- Adipokines, Inflammation, and Metabolic Diseases
- Adenosine and Purinergic Signaling
- Nicotinic Acetylcholine Receptors Study
- Thyroid Disorders and Treatments
- Histone Deacetylase Inhibitors Research
- Calcium signaling and nucleotide metabolism
Vanderbilt University
2010-2024
Center for Discovery
2021-2022
Vanderbilt University Medical Center
2015-2021
Oregon Health & Science University
2005-2010
Vollum Institute
2005
McGill University
1997-2004
Montreal General Hospital
1998-2004
The ascending prevalence of obesity in recent decades is commonly associated with soaring morbidity and mortality rates, resulting increased health-care costs decreased quality life. A systemic state stress characterized by low-grade inflammation pathological formation reactive oxygen species (ROS) usually manifests obesity. transcription factor nuclear erythroid-derived 2-like 2 (NRF2) the master regulator redox homeostasis plays a critical role resolution inflammation. Here, we show that...
Melanocortin-4 receptor (MC4R) is critical for energy homeostasis, and the paraventricular nucleus of hypothalamus (PVN) a key site MC4R action. Most studies suggest that leptin regulates PVN neurons indirectly, by binding to receptors in arcuate or ventromedial regulating release products like α-melanocyte-stimulating hormone (α-MSH), neuropeptide Y (NPY), glutamate, GABA from first-order onto cells. Here, we investigate mechanisms underlying regulation activity these under various...
Pharmacological manipulation of the melanocortin-3 receptor bidirectionally controls feeding, providing a therapeutic target for eating disorders.
Fasting-induced suppression of thyroid hormone levels is an adaptive response to reduce energy expenditure in both humans and mice. This mediated by the hypothalamic-pituitary-thyroid axis through a reduction TRH expressed neurons paraventricular nucleus hypothalamus (PVN). gene expression positively regulated leptin. Whereas decreased leptin during fasting lead expression, mechanisms underlying this process are still unclear. Indeed, evidence exists that PVN targeted indirectly via arcuate...
Like most homeostatic systems, adiposity in mammals is defended between upper and lower boundary conditions. While leptin melanocortin-4 receptor (MC4R) signaling are required for defending energy set point, mechanisms controlling boundaries less well understood. In contrast to the MC4R, deletion of MC3R does not produce measurable hyperphagia or hypometabolism under normal However, we demonstrate that bidirectionally responses external challenges, such as caloric restriction calorie-rich...
Depolarizing afterpotentials (DAPs) that follow action potentials in magnocellular neurosecretory cells (MNCs) are thought to underlie the generation of phasic firing, a pattern optimizes vasopressin release from neurohypophysis. Previous work has suggested DAP may result Ca(2+)-dependent reduction resting K(+) conductance. Here we examined effects flufenamic acid (FFA), blocker non-selective cation (CAN) channels, on DAPs and firing using intracellular recordings supraoptic MNCs superfused...
The properties and functional roles of the hyperpolarization-activated inward current (I(H)) in magnocellular neurosecretory cells (MNCs) were investigated during sharp microelectrode recordings from supraoptic neurons superfused explants rat hypothalamus. Under clamp, voltage responses to hyperpolarizing pulses featured depolarizing sags that abolished by I(H) blocker ZD 7288. subtraction steps recorded absence presence 7288 was used investigate I(H). Current-voltage analysis revealed...
The muscarinic acetylcholine receptor (mAChR) subtype 5 (M5) represents a novel potential target for the treatment of multiple addictive disorders, including opioid use disorder. Through chemical optimization several functional high-throughput screening hits, VU6019650 (27b) was identified as M5 orthosteric antagonist with high potency (human IC50 = 36 nM), selectivity (>100-fold against human M1-4) and favorable physicochemical properties systemic dosing in preclinical addiction models. In...
A slow posttrain afterhyperpolarization (sAHP) was studied in rat magnocellular neurosecretory cells (MNCs) vitro . The sAHP isolated from other afterpotentials by blocking the depolarizing afterpotential (DAP) with Cs + and medium (mAHP) apamin. amplitude increased logarithmically activity (∼3 mV per e -fold increase number of impulses) and, when firing stopped, decayed exponentially a time constant 2 sec. associated membrane conductance, its varied linearly voltage, reversing at K...
Neuropeptide W (NPW) is an anorectic peptide produced in the brain. Here, we showed that NPW was present several hypothalamic nuclei, including paraventricular nucleus, ventromedial lateral hypothalamus, and arcuate nucleus. expression significantly up-regulated leptin-deficient ob/ob leptin receptor-deficient db/db mice. The increase mice abrogated to control levels after replacement. Leptin induced suppressors of cytokine signaling-3 phosphorylation signal transducer activator...
Research Article12 July 2016Open Access Source DataTransparent process Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake Zhaiyi Zhang Department Molecular and Cellular Biochemistry, University Kentucky, Lexington, KY, USA Search for more papers by this author Manli Shen Paul J Gresch Pharmacology, Vanderbilt University, Nashville, TN, Masoud Ghamari-Langroudi Physiology & Biophysics, Alexander G Rabchevsky Spinal Cord Brain Injury, Center, Ronald B...
The effects of Cs + on the action potential, post‐train after‐hyperpolarization (AHP), Ca 2+ ‐dependent post‐spike depolarizing after‐potential (DAP) and phasic firing were examined during intracellular recordings from magnocellular neurosecretory cells (MNCs) in superfused rat hypothalamic explants. Extracellular reversibly inhibited (IC 50 , ≈1 mM) DAPs, associated after‐discharges, that followed brief spike trains each sixteen tested. Although bath application also provoked a small...
Abstract Leptin signals to regulate food intake and energy expenditure under conditions of normative homeostasis. The central expression function leptin receptor B (LepRb) have been extensively studied during the past two decades; however, mechanisms by which LepRb signaling dysregulation contributes pathophysiology obesity remains unclear. paraventricular nucleus hypothalamus (PVN) plays a crucial role in regulating balance as well neuroendocrine axes. PVN regard regulation physiological...
Energy stores in fat tissue are determined part by the activity of hypothalamic neurones expressing melanocortin-4 receptor (MC4R). Even a partial reduction MC4R expression levels mice, rats or humans produces hyperphagia and morbid obesity. Thus, it is great interest to understand molecular basis neuromodulation MC4R. The G protein-coupled that signals efficiently through GαS , this signalling pathway essential for normal function vivo. However, previous data from slice preparations...
Significance Cannabis is well known to regulate food intake, and cannabinoids increase the value of caloric non-caloric rewards, while also regulating homeostatic feeding. Here, we show that tonic endogenous cannabinoid signaling regulates melanocortin 4 receptor (MC4R) expressing paraventricular hypothalamic neurons through modulation their presynaptic inhibitory inputs in an energy state–dependent manner. Specifically, this 2-AG signal maximal during fasting collapses satiation. Impairing...
1 The effects of external Cs+ on magnocellular neurosecretory cells were studied during intracellular recordings from 93 supraoptic nucleus neurones in superfused explants rat hypothalamus. 2 Bath application 3–5 mm provoked reversible membrane depolarisation and increased firing rate all the tested. Voltage-current analysis revealed an increase resistance between −120 −55 mV. was greater below −85 mV than at more positive potentials. 3 Voltage-clamp showed that blocked...
Fasting-induced suppression of thyroid hormone levels is an adaptive response to reduce energy expenditure in both humans and mice. This mediated by the hypothalamic-pituitary-thyroid axis through a reduction TRH expressed neurons paraventricular nucleus hypothalamus (PVN). gene expression positively regulated leptin. Whereas decreased leptin during fasting lead expression, mechanisms underlying this process are still unclear. Indeed, evidence exists that PVN targeted indirectly via arcuate...