A5086527034- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Nicotinic Acetylcholine Receptors Study
- Nuclear Receptors and Signaling
- RNA regulation and disease
- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- Circadian rhythm and melatonin
- Tuberous Sclerosis Complex Research
- Polyamine Metabolism and Applications
- Memory and Neural Mechanisms
- Mast cells and histamine
- Genetics and Neurodevelopmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- GABA and Rice Research
- Phosphodiesterase function and regulation
- Mitochondrial Function and Pathology
- Protein Kinase Regulation and GTPase Signaling
- Hormonal and reproductive studies
- Cardiac electrophysiology and arrhythmias
- 14-3-3 protein interactions
- Neuroendocrine regulation and behavior
Wake Forest University
2017-2023
North Carolina Agricultural and Technical State University
2020-2023
The University of Texas at Austin
2013-2017
The University of Texas Southwestern Medical Center
2012
Group 1 metabotropic glutamate receptor (mGluR)-stimulated protein synthesis and long-term synaptic depression (mGluR-LTD) are altered in the mouse model of fragile X syndrome, Fmr1 knock-out (KO) mice. encodes mental retardation (FMRP), a dendritic RNA binding that functions, part, as translational suppressor. It is unknown whether how FMRP acutely regulates LTD and/or rapid new proteins required for LTD, such activity-regulated cytoskeletal-associated (Arc). The phosphatase PP2A...
A single injection of N-methyl-D-aspartate receptor (NMDAR) antagonists produces a rapid antidepressant response. Lasting changes in the synapse structure and composition underlie effectiveness these drugs. We recently discovered that antidepressants cause shift γ-aminobutyric acid (GABABR) signaling pathway, such GABABR activation shifts from opening inwardly rectifiying potassium channels (Kir/GIRK) to increasing resting dendritic calcium signal mammalian Target Rapamycin activity....
The fate of a memory, whether stored or forgotten, is determined by the ability an active tagged synapse to undergo changes in synaptic efficacy requiring protein synthesis plasticity-related proteins. A can be tagged, but without "capture" proteins, it will not long lasting forms plasticity (synaptic tagging and capture hypothesis). What "tag" how proteins are captured at synapses unknown. Ca2+/calmodulin-dependent kinase II α (CaMKIIα) critical learning memory synthesized locally neuronal...
Chronic peri-adolescent stress in humans increases risk to develop a substance use disorder during adulthood. Rats reared social isolation peri-adolescence (aSI; 1 rat/cage) period show greater ethanol and cocaine intake compared group housed (aGH; 4 rats/cage) rats. In addition, aSI rats have heightened dopamine response the nucleus accumbens (NAc) rewarding aversive stimuli. Furthermore, single pulse electrical stimulation slices containing NAc core elicits release Here, we further...
Abstract Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, molecular/synaptic pathways are shared by alcohol and antidepressants unknown. In current study, acute exposure ethanol produced antidepressant anxiolytic behaviours. To understand functional basis of these behaviours, we examined a molecular pathway is activated rapid antidepressants. Ethanol, like antidepressants, alters...
Many biological processes involve the mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Thus, challenge deciphering mTORC1-mediated functions during normal and pathological states in central nervous system is challenging. Because mTORC1 at core translation, we have investigated function global regional protein expression. Activation has been generally regarded to promote translation. Few but recent works shown that suppression can also local synthesis. Moreover, excessive...
Dysregulation of biological rhythms plays a role in wide range psychiatric disorders. We report mechanistic insights into the rapid dopamine signals and cholinergic interneurons (CINs) working concert rodent striatum. These mediate diurnal variation conditioned responses to reward-associated cues. that signal-to-noise ratio varies according time day phasic are magnified during middle dark cycle rats. show CINs provide mechanism for by serving as gain function adjusts across day. also cues...
L-type voltage-gated calcium (Ca 2+ ) channels (L-VGCC) dysfunction is implicated in several neurological and psychiatric diseases. While a popular therapeutic target, it unknown whether molecular mechanisms leading to disrupted L-VGCC across neurodegenerative disorders are conserved. Importantly, integrate synaptic signals facilitate plethora of cellular mechanisms; however, that regulate channel density subcellular compartmentalization understudied. Herein, we report disease models with...
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as regulator mRNA translation. Recent studies suggest that mTORC1 may also serve a local, voltage sensor in the postsynaptic region neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize activity state dynamically regulates local membrane potential by promoting repressing protein synthesis select mRNAs. Our hypothesis suggests uses positive negative feedback pathways, branch-specific manner, to...
Abstract Tuberous sclerosis complex (TS) is a dominant, multisystem disorder with devastating neurological symptoms. Approximately 85% of TS patients suffer from epilepsy over their lifespan and roughly 25-50% those develop Autism Spectrum Disorder (1, 2). Current seizure therapies are effective in some, but not all, often have significant risk factors associated use 3). Thus, there critical need for new medication development or drug repositioning. Herein, we leveraged proteomic signatures...
Alzheimer's Disease (AD) is a complex neurodegenerative disorder of the synapse, characterized by accumulation amyloid beta plaques and neurofibrillary tangles. We have recently shown that Parkinson Protein 7, DJ-1, upregulated mTORC1 activity, translational hub predicted to coordinate expression population synaptic proteins (Niere et al., 2016). This cellular function DJ-1 mediated through its RNA-binding properties, yet many target mRNAs are unidentified, effects this protein-mRNA...
Abstract Background Hyperexcitability and glutamate excitotoxicity are the primary contributors towards synapse loss in Alzheimer’s disease (AD). The goal of this project is to examine how other neurotransmitter systems, such as inhibitory GABAergic system, responding hyperexcitability AD. Therefore, we examined role metabotropic GABA B receptors (GABA Rs) loss. Methods Primary hippocampal neurons were cultured from both wildtype (WT) transgenic APP/PS1 mice. In addition, treatment...
Abstract Background Alzheimer’s Disease (AD) is a progressive cognitive disorder where synapse loss has been well documented. Identifying and restoring molecular targets that are involved in crucial balanced synaptic function communication. FMRP an RNA‐binding protein essential for formation stability, understudied AD. Understanding how may be dysregulated at the level AD integral developing treatments Method RNA‐immunoprecipitation of DJ‐1 was performed to detect whether associates with...
Abstract Background L‐type voltage‐dependent Ca 2+ channels (L‐VGCC) dysfunction is implicated in several neurological and psychiatric diseases. While a popular therapeutic target, it unknown if molecular mechanisms leading to disrupted L‐VGCC across neurodegenerative disorders conserved. Importantly, integrate synaptic signals facilitate plethora of cellular mechanisms; however, that regulate channel density subcellular compartmentalization are understudied. Method The following methods...
Abstract Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over past twenty years, a growing body evidence has revealed distinct functional roles dorsal (dHC) and ventral (vHC) subregions, with dHC being primarily involved spatial learning memory vHC regulating anxiety-and depressive-like behaviors. Notably, to our knowledge, no rodent examined effects chronic ethanol exposure on synaptic transmission along dorsal/ventral...
Alzheimer's Disease (AD) is a progressive synaptic disorder and the 6th leading cause of death in United States. To date, there still no effective long term therapy or cure. Parkinson Protein 7 (DJ-1) protein that was recently identified as potential biomarker for AD. Our recent work has predicted DJ-1 translational hub, an RNA binding can potentially determine expression other proteins important learning memory. Of note, DJ-1's RNA-binding properties, mRNA-targets, physiological functions...
Abstract L-type voltage-dependent Ca 2+ channels (L-VDCC) integrate synaptic signals to facilitate a plethora of cellular mechanisms. L-VDCC dysfunction is implicated in several neurological and psychiatric diseases. Despite their importance, upstream activity that regulate channel density, however, are poorly defined. In disease models with overactive mammalian target rapamycin complex 1 (mTORC1) signaling (or mTORopathies), including tuberous sclerosis (TS) Alzheimer’s (AD), we report...
Abstract Background Synapse loss is well‐documented and underlies cognitive decline in Alzheimer’s disease (AD) other comorbid neuropsychiatric disorders such as depression. To date, few molecular targets mechanisms are identified to restore/maintain healthy synapses AD. AD depression both have disrupted mechanistic/mammalian target of rapamycin complex 1 (mTORC1) activity. Since mTORC1 involved protein synthesis, disruptions activity creates an imbalance between mRNA translation repression...