Medicine and Health Sciences Commons^™

How Does Schizophrenia Affect The Expression Of Alpha 7 Nicotinic Acetylcholine Receptors In The Brain?, Shruti Varshney, Nimish Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is a psychiatric disorder with a pathophysiology that has not yet been fully understood. This mental illness is characterized by disruptions in cognition, social activity, affect, and perception, and affects approximately 0.085% of individuals worldwide. The Alpha 7 Nicotinic Acetylcholine Receptor (α7nAChR) has been connected to auditory function gating deficits. The purpose of this review is to understand the current literature in how the levels of α7nAChR expression and function are affected by SZ, information that could be used to develop therapies to modulate auditory hallucinations in patients with SZ. A literature search was conducted for peer-reviewed journal …

Alpha 7 Nicotinic Acetylcholine Receptor Expression In The Hippocampus Of Patients With Schizophrenia, Shruti Varshney, Ananya Nethikunta, Minjal Patel, Mary Kosciuk, Randel L. Swanson, Venkat Venkataraman, Robert Nagele, Eric Goldwaser, Nimish Acharya

Rowan-Virtua Research Day

Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research …

Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino

Farber Institute for Neuroscience Faculty Papers

Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …

An Erp Measure Of Non-Conscious Memory Reveals Dissociable Implicit Processes In Human Recognition Using An Open-Source Automated Analytic Pipeline, Richard J. Addante, Javier Lopez-Calderon, Nathan Allen, Carter Luck, Alana Muller, Lindsey Sirianni, Cory S. Inman, Daniel L. Drake

Psychology Student Publications

Non-conscious processing of human memory has traditionally been difficult to objectively measure and thus understand. A prior study on a group of hippocampal amnesia (N = 3) patients and healthy controls (N = 6) used a novel procedure for capturing neural correlates of implicit memory using event-related potentials (ERPs): old and new items were equated for varying levels of memory awareness, with ERP differences observed from 400 to 800 ms in bilateral parietal regions that were hippocampal-dependent. The current investigation sought to address the limitations of that study by increasing the sample of healthy subjects (N = …

Glutamate, And Its Relationship To Task-Induced Functional Connectivity In The Human Brain: A Focus On Schizophrenia, Kathleen Liu Young, John Kopchick, Jeffrey Stanley, Vaibhav Diwadkar

Medical Student Research Symposium

Glutamate is the brain’s major excitatory neurotransmitter mediating both neuroplasticity and network function (Zhou & Danbolt, 2014). Basal glutamate (Glu) measured using proton magnetic resonance spectroscopy (1H-MRS) provides insight into a region’s density of neuropil related to the glutamatergic system. Moreover, given the role of glutamate in mediating brain network function, Glu levels may play a role in the brain’s functional connectivity (FC), which is typically estimated from functional magnetic resonance imaging (fMRI) time series data. These questions converge when considering the clinical syndrome of schizophrenia (SCZ). Patients with SCZ show abnormalities in basal Glu in the hippocampus and prefrontal …

Context, Goals, And Operant Behavior: The Role Of The Prelimbic Cortex And Associated Neural Circuitry, Callum Mark Piper Thomas

Graduate College Dissertations and Theses

Operant (instrumental) conditioning is a laboratory model of voluntary behavior. In its simplest form, performing a particular response, such as a lever press, leads to delivery of a reinforcing outcome (e.g., a sucrose pellet). Operant behaviors can be associated with preceding stimuli (“habits”) or outcomes (“goal-directed actions”). A factor that influences performance of operant behaviors is the context in which they are learned. Contexts can be defined as background stimuli that are present during behavior. For example, eating dessert may occur in the context of a restaurant and the sated feeling of a finished meal. The context for eating dessert, …

Differential Regulation Of Gene Expression Pathways With Dexamethasone And Acth After Early Life Seizures., Jeffrey L Brabec, Mohamed Ouardouz, J Matthew Mahoney, Rod C Scott, Amanda E Hernan

Faculty Research 2022

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients' quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even …

The Effects Of Astrocytic Derived Insulin-Like Growth Factor (Igf-1) On Cognition And Astrocytes, Destiny Wilson

Honors Theses

Insulin-like growth factor 1 (IGF-1) is a neuroendocrine signaling hormone that plays a vital role in growth and development, as well as learning and memory. Inhibition of this hormone results in cognitive impairments like those seen with age-related decline. While a majority of research has focused on the role of IGF-1 on neurons, the role of astrocytes still needs to be explored. Our research investigates how astrocytes and cognition are affected as a result of direct regulation of localized IGF-1 production in early development and after puberty. Preliminary studies in our laboratory established a connection between IGF-1 and glial fibrillary …

Therapeutic Treatment With The Anti-Inflammatory Drug Candidate Mw151 May Partially Reduce Memory Impairment And Normalizes Hippocampal Metabolic Markers In A Mouse Model Of Comorbid Amyloid And Vascular Pathology, David J. Braun, David K. Powell, Christopher J. Mclouth, Saktimayee M. Roy, D. Martin Watterson, Linda J. Van Eldik

Neuroscience Faculty Publications

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop …

Diabetes Mellitus Affects Working Memory, Dylone C. Braganza, Emmanuel Flores, Lauren A. Crew, Ryan A. Wirt, Andrew A. Ortiz, Adam M. Mcneela, Jefferson W. Kinney, James M. Hyman

Spectra Undergraduate Research Journal

Alzheimer’s disease (AD) degrades the brain’s ability to remember, think, and carry out tasks. The exact cause is not known, but several risk factors have been identified, including diabetes mellitus (DM). DM causes elevated blood sugar levels due to reduced insulin production in the pancreas. The linkage between elevated glucose levels and the behavioral impairments are not fully understood, which was the focus of this study. Rats were trained to alternate directions in a maze to receive a reward on consecutive trials. After training, five rats were injected with streptozotocin (STZ), which induces hyperglycemia by injuring pancreatic beta cells. Three …

Placenta-Expanded Stromal Cell Therapy In A Rodent Model Of Simulated Weightlessness, Amber M. Paul, Linda Rubinstein, Charles Houseman, Metadel Abegaz, Steffy Tabares Ruiz

Publications

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of …

Acute Systemic Inflammatory Response Alters Transcription Profile Of Genes Related To Immune Response And Ca 2+ Homeostasis In Hippocampus; Relevance To Neurodegenerative Disorders, Grzegorz A. Czapski, Yuhai Zhao, Walter J. Lukiw, Joanna B. Strosznajder

School of Medicine Faculty Publications

Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 …

Wild Mice With Different Social Network Sizes Vary In Brain Gene Expression, Patricia C. Lopes, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background

Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parent-offspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution …

Levels Of Parp1-Immunoreactivity In The Human Brain In Major Depressive Disorder, Aamir Shaikh

Undergraduate Honors Theses

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search …

The Effects Of Different Doses Of Diclofenac Sodium On Newborn Rat Hippocampus Exposed During The Third Trimester, Ebru Eli̇bol, Süleyman Kaplan, Gamze Altun, Abdurrahman Aksoy, Berri̇n Zuhal Altunkaynak

Turkish Journal of Veterinary & Animal Sciences

The main aim of the present study was to examine the neurotoxic effects of prenatal exposure to varying doses of diclofenac sodium (DS) on the rat hippocampus. Twenty-eight Wistar albino adult female rats weighing 280-300 g were initially used for pregnancy. When vaginal plaques were seen in female rats, it was accepted as the 0th day of pregnancy. Female rats were divided into five main groups; pure control, saline, low dose DS (3.6 mg/kg), moderate dose DS (9 mg/kg), and high dose DS (18 mg/kg). They were exposed to these treatments during their gestation. After birth, all newborn male rats …

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Publications

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …

Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang

Theses and Dissertations (ETD)

The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Changes In Hippocampal-Anterior Cingulate Cortex Interactions During Remote Memory Recall, Ryan A. Wirt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Spatial memory is an important cognitive process that relies on extensive neural networks throughout the brain. The hippocampus (HC) is important for the formation of these memories but over time, in a process referred to as consolidation, recall becomes increasingly reliant on other brain areas. The anterior cingulate cortex (ACC), a region within the medial prefrontal cortex, is important for spatial learning, spatial working memory, and remote memory recall, but the mechanisms underlying recall processes are still unknown. To better understand the role of the ACC and HC during memory recall, we introduced rodents into a series of spatially and …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

Neuroprotective Effects Of Melatonin And Celecoxib Against Ethanol-Induced Neurodegeneration: A Computational And Pharmacological Approach, Lina T. Al Kury, Alam Zeb, Zain Ul Abidin, Nadeem Irshad, Imran Malik, Arooj Mohsin Alvi, Atif Ali Khan Khalil, Sareer Ahmad, Muhammad Faheem, Arif Ullah Khan, Fawad Ali Shah, Shupeng Li

All Works

© 2019 Al Kury et al. This work is published and licensed by Dove Medical Press Limited. Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. Methods: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. Results: Homology modeling was performed to build 3-D …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Baseline White Matter Hyperintensities And Hippocampal Volume Are Associated With Conversion From Normal Cognition To Mild Cognitive Impairment In The Framingham Offspring Study., Katherine J Bangen, Sarah R Preis, Lisa Delano-Wood, Philip A Wolf, David J Libon, Mark W Bondi, Rhoda Au, Charles Decarli, Adam M Brickman

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up.

METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified.

RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion …

Disruption Of Hippocampal Multisynaptic Networks By General Anesthetics., Min-Ching Kuo, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

METHODS: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Spontaneous local field potentials and evoked field potentials were recorded in freely behaving rats before (baseline) and after various doses of isoflurane (0.25 to 1.5%) and sodium pentobarbital (10 mg/kg intraperitoneal).

RESULTS: Monosynaptic population excitatory postsynaptic potentials at the …

Acute Treatment With Doxorubicin Affects Glutamate Neurotransmission In The Mouse Frontal Cortex And Hippocampus, Theresa Currier Thomas, Joshua A. Beitchman, Francois Pomerleau, Teresa Noel, Paiboon Jungsuwadee, D. Allan Butterfield, Daret K. St. Clair, Mary Vore, Greg A. Gerhardt

Spinal Cord and Brain Injury Research Center Faculty Publications

Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25 mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) …

Using Enzyme-Based Biosensors To Measure Tonic And Phasic Glutamate In Alzheimer's Mouse Models, Holly C. Hunsberger, Sharay E. Setti, Ryan T. Heslin, Jorge E. Quintero, Greg A. Gerhardt, Miranda N. Reed

Neuroscience Faculty Publications

Neurotransmitter disruption is often a key component of diseases of the central nervous system (CNS), playing a role in the pathology underlying Alzheimer's disease, Parkinson's disease, depression, and anxiety. Traditionally, microdialysis has been the most common (lauded) technique to examine neurotransmitter changes that occur in these disorders. But because microdialysis has the ability to measure slow 1-20 minute changes across large areas of tissue, it has the disadvantage of invasiveness, potentially destroying intrinsic connections within the brain and a slow sampling capability. A relatively newer technique, the microelectrode array (MEA), has numerous advantages for measuring specific neurotransmitter changes within discrete …

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca²⁺]_i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca²⁺]_i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca²⁺ channels.

Results

In CA3 pyramidal neurons, kainic …