Medical Neurobiology Commons^™

Dha Shortage Causes The Early Degeneration Of Photoreceptors And Rpe In Mice With Peroxisomal Β-Oxidation Deficiency, Daniëlle Swinkels, Sai Kocherlakota, Yannick Das, Adriaan D. Dane, Eric J.M. Wever, Frédéric M. Vaz, Nicolas G. Bazan, Paul P. Van Veldhoven, Myriam Baes

School of Medicine Faculty Publications

PURPOSE. Patients deficient in peroxisomal β-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, develop retinopathy present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2−/−), also show early-onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration of Mfp2−/− mice. METHODS. Mfp2+/− breeding pairs and their offspring were fed a 0.12% DHA …

The Effect Of Intervention For Improving Colonoscopy Quality Is Associated With The Personality Traits Of Endoscopists, Guiyuan Xiang, Jiangtao Li, Qinlu Lin, Yili Zhang, Yuqin Ding, Xiaofeng Guo, Qianru Pan, Qiongxiang Liu, Xiangjin Fu, Ying Yang, Wenfang Han, Yong Fang

Faculty, Staff and Student Publications

Highlights

• HMT promoted the binding between starch, protein and lipid.
• • The gelatinization viscosity of HMT rice flour was sharply increased when the proteins were removed.
• • Proteins played a critical role in the physicochemical changes of HMT rice flour.

This study investigated the effect of removing proteins, lipids and starch on the structure, physicochemical properties and digestion properties of rice flour (with 30% moisture) treated with heat moisture treatment (HMT). According to the results, HMT caused the adhesion and agglomeration of the rice flour, promoted the binding between starch, protein and lipid molecular chains and led to the formation …

Ca2+-Regulated Expression Of High Affinity Methylaminoisobutryic Acid Transport In Hippocampal Neurons Inhibited By Riluzole And Novel Neuroprotective Aminothiazoles, Jeffrey D. Erickson, Thomas Kyllo, Heike Wulff

School of Medicine Faculty Publications

High affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca2+-regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K+ stimulated transport activity that is inhibited by staurosporine. 4-AP-stimulated spontaneous and PMA-stimulated high K+-induced transport is not present at 7 days in vitro (DIV) and is maximal by DIV∼21. The relative affinity for MeAIB is similar …

Whole Genome Sequence Data Implicate Rbfox1 In Epilepsy Risk In Baboons, Mark Z. Kos, Melanie A. Carless, Lucy Blondell, Mary M. Leland, Koyle D. Knape, Harald H. H. Goring, Charles A. Szabo

Research Symposium

Background: Baboons exhibit a genetic generalized epilepsy (GGE) that resembles juvenile myoclonic epilepsy and may represent a suitable genetic model for human epilepsy. The genetic underpinnings of epilepsy were investigated in a baboon colony at the Southwest National Primate Research Center (San Antonio, TX) through the analysis of whole-genome sequence (WGS) data.

Methods: Baboon WGS data were obtained for 38 cases and 19 healthy controls from the NCBI Sequence Read Archive and, after standard QC filtering, two subsets of variants were examined: (1) 20,881 SNPs from baboon homologs of 19 candidate GGE genes; and (2) 36,169 protein-altering SNPs. Association tests …

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Regulation Of Syntaxin3b-Mediated Membrane Fusion By T14, Munc18, And Complexin, Rajkishor Nishad, Miguel Betancourt-Solis, Himani Dey, Ruth Heidelberger, James A Mcnew

Faculty, Staff and Student Publications

Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B …

Can Alternative Medical Methods Evoke Neuro-Functional Somatosensory Responses? A Case Study Suggesting Functional Improvement, Alhasn Otaif, Mashan E. Alshammari, Christine G. Gerin

Research Symposium

Somatosensory pathways act as the avenue in transferring information concerning the body and its interaction with the external environment to the brain. We aim to demonstrate that through studying somatosensory, motor cortical and subcortical networks, we can explain functional recovery after stimulations applied as an alternative medical treatment. Those stimulations might have evidenced neural pathways and networks important in recovery of function. Materials and methods: The de-identified medical reports of nine patients with initial presentations of cerebral trauma or stroke inducing paralysis were studied.These included the alternative treatments they received and other available materials such as videos and photographs. Patients …

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …

Enhanced Presynaptic Mitochondrial Energy Production Is Required For Memory Formation, Erica L Underwood, John B Redell, Kimberly N Hood, Mark E Maynard, Michael Hylin, M Neal Waxham, Jing Zhao, Anthony N Moore, Pramod K Dash

Faculty, Staff and Student Publications

Some of the prominent features of long-term memory formation include protein synthesis, gene expression, enhanced neurotransmitter release, increased excitability, and formation of new synapses. As these processes are critically dependent on mitochondrial function, we hypothesized that increased mitochondrial respiration and dynamics would play a prominent role in memory formation. To address this possibility, we measured mitochondrial oxygen consumption (OCR) in hippocampal tissue punches from trained and untrained animals. Our results show that context fear training significantly increased basal, ATP synthesis-linked, and maximal OCR in the Shaffer collateral-CA1 synaptic region, but not in the CA1 cell body layer. These changes were …

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …

Cerebellar Interneurons Control Fear Memory Consolidation Via Learning-Induced Hcn Plasticity, Kathryn Lynn Carzoli, Georgios Kogias, Jessica Fawcett-Patel, Si-Qiong J. Liu

School of Medicine Faculty Publications

While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation. The fear conditioning paradigm produces a lasting reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in these interneurons. This change increases intrinsic membrane excitability and enhances the response to synaptic stimuli. HCN loss is driven …

Causal Inference Methods For Estimation Of Survival And General Health Status Measures Of Alzheimer’S Disease Patients, Ehsan Yaghmaei

Computational and Data Sciences (PhD) Dissertations

Identifying optimal treatment options with respect to survival of Alzheimer's disease patients is crucially important and previously uninvestigated research question. Our objective was to estimate the causal effects of the most prevalent classes of Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on Survival and General Health Status Measures of Alzheimer's disease patients for the first five years after initial diagnosis. We carried out a thorough causal inference study using doubly robust estimators, nonparametric bootstrap confidence intervals, Bonferroni corrections for multiple comparisons and analyzing one of the largest high-quality medical databases containing millions of de-identified electronic health records …

The Genetic Relationship Between Peripheral Inflammation And Alzheimer’S Disease, Davis Cammann

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and has become an ever-present problem in aging populations. An increasing body of evidence suggests that neuroinflammation is one of the key drivers of AD pathology. One overlooked contributor to this burden is peripheral inflammation throughout the body. Due to increased permeability of the blood-brain-barrier (BBB) in older age, inflammatory plasma proteins and immune cells infiltrate the CNS and drive neuroinflammation through interactions with neurons and glia. In addition, age-related changes in the composition of gut microbiome taxa lead to increased gut permeability and inflammatory burden. Because inflammatory factors are …

Epileptic Seizure Classification Using Image-Based Data Representation, Amber Surles

Graduate Theses and Dissertations (2019 - present)

Epilepsy is a recurrence of seizures caused by a disorder of the brain in over 3.4 million people nationwide. Some people are able to predict their seizures based off prodrome, which is an early sign or symptom that usually resembles mood changes or a euphoric feeling even days to an hour before occurrence. Consequently, the natural instincts of the body to react to an upcoming attack lends credence to the existence of a pre-ictal state that precedes seizure episodes. Physicians and researchers have thus sought for an automated approach for predicting or detecting seizures.

In this research, we evaluate the …

An Observational Study To Develop A Predictive Model For Bacterial Pneumonia Diagnosis In Severe Covid-19 Patients-C19-Pneumoscore, Eloisa Sofia Tanzarella, Joel Vargas, Marco Menghini, Stefania Postorino, Francesca Pozzana, Maria Sole Vallecoccia, Francesco Lorenzo De Matteis, Federico Franchi, Amato Infante, Luigi Larosa, Maria Antonietta Mazzei, Salvatore Lucio Cutuli, Domenico Luca Grieco, Alessandra Bisanti, Simone Carelli, Gianmarco Lombardi, Edoardo Piervincenzi, Gabriele Pintaudi, Tommaso Pirronti, Mario Tumbarello, Massimo Antonelli, Gennaro De Pascale

Faculty, Staff and Student Publications

In COVID-19 patients, antibiotics overuse is still an issue. A predictive scoring model for the diagnosis of bacterial pneumonia at intensive care unit (ICU) admission would be a useful stewardship tool. We performed a multicenter observational study including 331 COVID-19 patients requiring invasive mechanical ventilation at ICU admission; 179 patients with bacterial pneumonia; and 152 displaying negative lower-respiratory samplings. A multivariable logistic regression model was built to identify predictors of pulmonary co-infections, and a composite risk score was developed using β-coefficients. We identified seven variables as predictors of bacterial pneumonia: vaccination status (OR 7.01; 95% CI, 1.73-28.39); chronic kidney disease …

Long-Term Bilateral Neuromuscular Function And Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction, Payam Zandiyeh, Lauren R Parola, Meggin Q Costa, Madalyn J Hague, Janine Molino, Braden C Fleming, Jillian E Beveridge

Faculty, Staff and Student Publications

Neuromuscular function is thought to contribute to posttraumatic osteoarthritis (PTOA) risk in anterior cruciate ligament (ACL)-reconstructed (ACLR) patients, but sensitive and easy-to-use tools are needed to discern whether complex muscle activation strategies are beneficial or maladaptive. Using an electromyography (EMG) signal analysis technique coupled with a machine learning approach, we sought to: (1) identify whether ACLR muscle activity patterns differed from those of healthy controls, and (2) explore which combination of patient outcome measures (thigh muscle girth, knee laxity, hop distance, and activity level) predicted the extent of osteoarthritic changes via magnetic resonance imaging (MRI) in ACLR patients. Eleven ACLR …

Caudal Dmn Neurons Innervate The Spleen And Release Cart Peptide To Regulate Neuroimmune Function, Nobuhide Kobori, Anthony N Moore, John B Redell, Pramod K Dash

Faculty, Staff and Student Publications

BACKGROUND: Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, …

Cortex-Wide Neural Dynamics Predict Behavioral States And Provide A Neural Basis For Resting-State Dynamic Functional Connectivity, Somayeh Shahsavarani, David N Thibodeaux, Weihao Xu, Sharon H Kim, Fatema Lodgher, Chinwendu Nwokeabia, Morgan Cambareri, Alexis J Yagielski, Hanzhi T Zhao, Daniel A Handwerker, Javier Gonzalez-Castillo, Peter A Bandettini, Elizabeth M C Hillman

Faculty, Staff and Student Publications

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across …

Interleukin-1 Signaling And Alcohol-Induced Cortical Dysfunction, Florence Varodayan, Amanda Pahng, Tony Davis, T. Nadav, I. Polis, C.C. Cates-Gatto, Michal Bajo, Michael D. Burkart, Scott Edwards, Amanda J. Roberts, Marisa Roberto

School of Medicine Faculty Publications

Alcoholism and Stress: A Framework for Future Treatment Strategies; Volterra, Italy; May 16-19, 2023

The Interaction Between Host G3bp And Viral Nucleocapsid Protein Regulates Sars-Cov-2 Replication, Zemin Yang

Theses and Dissertations (ETD)

G3BP1/2 are RNA-binding proteins that promote condensation to form stress granules in response to various cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP-N interaction in the context of viral infection have remained unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively disrupt their interaction. We found that mutation of N-F17 led to selective loss of interaction with G3BP1 and consequent failure of …