Life Sciences Commons^™

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Analytical Modeling Of A Communication Channel Based On Subthreshold Stimulation Of Neurobiological Networks, Alireza Khodaei

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the others …

Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Both insulin signaling disruption and Ca²⁺ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca²⁺-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca²⁺-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in …

Identification Of Changes In Neuronal Function As A Consequence Of Aging And Tauopathic Neurodegeneration Using A Novel And Sensitive Magnetic Resonance Imaging Approach, Sarah N. Fontaine, Alexandria Ingram, Ryan A. Cloyd, Shelby E. Meier, Emily Miller, Danielle N. Lyons, Grant K. Nation, Elizabeth Mechas, Blaine Weiss, Chiara Lanzillotta, Fabio Di Domenico, Frederick A. Schmitt, David K. Powell, Moriel H. Vandsburger, Jose Francisco Abisambra

Sanders-Brown Center on Aging Faculty Publications

Tauopathies, the most common of which is Alzheimer’s disease (AD), constitute the most crippling neurodegenerative threat to our aging population. Tauopathic patients have significant cognitive decline accompanied by irreversible and severe brain atrophy, and it is thought that neuronal dysfunction begins years before diagnosis. Our current understanding of tauopathies has yielded promising therapeutic interventions but have all failed in clinical trials. This is partly due to the inability to identify and intervene in an effective therapeutic window early in the disease process. A major challenge that contributes to the definition of an early therapeutic window is limited technologies. To address …

Girk2 And Gababr1 Downregulate In Response To Ttx As Girk2, Gababr1, And Gababr2 Are Not Affected By Bc Treatment, Staci E. Hammer, Amanda Weiss, Hee Jung Chung

PRECS student projects

Homeostatic plasticity is the response neurons undergo to regulate changes in excitability levels and bring the cells back to homeostasis. Research on homeostatic plasticity at the molecular level can lead to improved treatments for neurological diseases such as epilepsy, Alzheimer's, and schizophrenia. The research featured in this poster looks at the response of GIRK (G protein-gated inwardly rectifying potassium) channels and GABAb (gamma-amniobutyric acid) receptors to neurotoxins, tetrodotoxin (TTX) or bicuculline (BC).

Prolonged activity blockade of 48 hour TTX treatment significantly reduced GABABR1 and GIRK2 expression. This supports the idea that because these two proteins inhibit action potentials, there will …

Examining The Neuronal Dopaminergic Pathway Underlying Sleep Behavior And Related Dopamine Sleep Disorders, Mary Beth Putz

Undergraduate Honors Theses

The human brain is an extremely complex organ with approximately 100 billion different neurons that are constantly sending and receiving messages. These messages are sent using the chemical messengers of the brain: neurotransmitters and neuromodulators. Mechanisms of neural control of sleep are substantially conserved across species. Evidence from multiple animal models including flies, zebrafish, and mice shows that the arousal, or wake phase, is regulated by conserved neuromodulators such as dopamine, norepinephrine, and serotonin. Since these neurotransmitter systems are distributed throughout the brain and sub-serve many functions in addition to sleep, the precise circuit mechanisms by which these neurotransmitters regulate …

Electrophysiological And Morphological Characterization Of Neurons In The Granular Retrosplenial Cortex, Andrew Nicholas Nye

Theses and Dissertations

The retrosplenial cortex (RSC) is a centrally located brain region that has reciprocal connections with several brain regions important for memory, including the prefrontal cortex, para-hippocampal region, hippocampal formation, and rhinal cortices. The RSC is also well connected with structures important for sensory processing, including the parietal cortex, thalamus, and visual cortices. Due to this connectivity, and early evidence that suggests the RSC plays a critical role in learning and memory, the region has recently gained much more research attention. Early studies found that patients with brain damage that includes the RSC have difficulty with verbal and visual information, retrieving …

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 …

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABA_B receptor can suppress the ionotropic GABA_A receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …