Neurosciences Commons^™

Analyzing The Neuroprotective Effects Of Phytoestrogens And Aromatase On Male Zebra Finch Cerebellum Post Lesion, Tony Irovic, Grace Thompson, Lainy B. Day

Neuroscience Research Showcase

(All authors are affiliated with Interdisciplinary Studies: Neuroscience, Department of Biology, Interdisciplinary Neuroscience Minor, University of Mississippi)

Introduction:

• Estradiol (E2) & aromatase (AROM) are neuroprotective
• AROM enzymatically converts testosterone (T) into E2
• E2 alters testicular function and increases stroke and cancer risk
• Phytoestrogens, such as genistein (GEN), are plant derived compounds that have a similar chemical structure to E2 and some E2 -like effects
• GEN may possess the neuroprotective effects of E2 while not having the negative effects
• Zebra finch (ZF) brains are highly plastic, and the cerebellum (CB) has low AROM constitutively
• The CB has high levels of estrogen …

Volumetric Changes In Cerebellar Transverse Zones: Age And Sex Effects In Health And Neurological Disorders, Farshid Ghiyamihoor, Payam Paymani, Jarrad Perron, Azam Asemi-Rad, Mehdi Marzban, Aashka Mohite, Karen Ardila, Bara Aljada, Asghar Marzban, Mehnosh Toback, Sherif Eltonsy, Ji Hyun Ko, Tabrez J Siddiqui, Christopher J Steele, Jiming Kong, Mario Manto, M Ethan Macdonald, Jason S Gill, Roy V Sillitoe, Fuat Balcı, Iman Beheshti, Hassan Marzban

Duncan NRI Faculty and Staff Publications

Cerebellar volumetric changes are intricately linked to aging, with distinct patterns across its transverse zones, the functional subdivisions characterized by unique cytoarchitectural and connectivity profiles. Despite research efforts, the cerebellar aging process in health and neurological disorders remains poorly understood. In this study, we investigated the effects of age and sex on total cerebellum, transverse zone, and lobule volumes using MRI data from over 45,000 participants compiled from six neuroimaging datasets. We also propose a framework for estimating cerebellum age as an indicator of cerebellar health. Significant age‐dependent volume reductions were observed across transverse zones, with the …

The Effects Of Estradiol And Genistein On Cerebellar Neuroprotection In Zebra Finches, Grace Thompson, Tony Irovic, Lainy B. Day

Neuroscience Research Showcase

Poster presented at Annual Neuroscience Showcase University of Mississippi related to neuroprotection of genistein and estradiol post-brain lesion.

Investigating The Effects Of Sex And Estrous Cycle On The Incubation Of Cue-Induced Oxycodone Craving, Bhumiben Pradipkumar Patel

Theses and Dissertations

The overprescription and misuse of opioids like oxycodone has played a significant role in the ongoing opioid crisis. While effective painkillers, drugs like oxycodone are also reinforcing and often misused. While sex and ovarian hormones can impact the analgesic effects of these drugs, the impact of these factors on oxycodone reinforcement are not fully understood. This relationship between ovarian hormones and opioid reward is further complicated by the fact that opioid use can disrupt ovarian hormone levels and produce reproductive cycle irregularities. Using a rat model of drug craving and relapse vulnerability, we found that chronic oxycodone exposure produced reproductive …

An Open-Label Study Evaluating The Safety And Efficacy Of Amo-01 For The Treatment Of Seizures In Phelan-Mcdermid Syndrome, Tess Levy, J Lloyd Holder, Joseph P Horrigan, Michael F Snape, Alison Mcmorn, Christina Layton, Hailey Silver, Kate Friedman, Hannah Grosman, Slayton Underwood, Danielle Halpern, Jessica Zweifach, Paige M Siper, Alexander Kolevzon

Duncan NRI Faculty and Staff Publications

Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene. Approximately 25% of individuals with PMS have epilepsy. Treatment of epilepsy in PMS may require multiple anticonvulsants, and in a minority of cases, seizures remain poorly controlled. Converging lines of evidence in different experimental models indicate that the Ras-ERK pathway is implicated in the pathophysiology of seizure generation and neurobehavioral symptoms in PMS. The goal of this study was to evaluate the safety, tolerability, and efficacy in treating seizures in adults and adolescents with PMS using AMO-01, a Ras-ERK pathway inhibitor. A single 6-hour intravenous infusion …

Phosphotungstic Acid Staining To Visualize The Vagus Nerve Perineurium Using Micro-Ct, Aniruddha R. Upadhye, Jennifer Coleman, Michael W. Jenkins, David Wilson, Andrew J. Shoffstall

Faculty Scholarship

Background and Purpose: Peripheral nerve stimulation is approved by the US Food and Drug Administration for treating various disorders, but it is often limited by side effects, highlighting the need for a clear understanding of fascicular and fiber organization to design selective therapies. Micro-CT imaging of contrast-stained nerves enables the visualization of tissue microstructures, such as the fascicular perineurium and vasculature. In this work, we evaluated phosphotungstic acid (PTA) as a contrast agent and assessed its compatibility with downstream histology. Methods: Human vagus nerve samples were collected from three embalmed cadavers and subjected to three different staining methods, followed by …

Hdac5 Enzymatic Activity Regulates Scn4b Expression To Control Relapse-Like Cocaine Seeking, Daniel J. Wood

MUSC Theses and Dissertations

Substance Use Disorder (SUD) is a relapsing disorder characterized by repeated seeking and use of psychoactive substances despite negative consequences to the individual. Epigenetic changes within the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) are thought to underly the lasting propensity to relapse in SUD. The epigenetic enzyme histone deacetylase 5 (HDAC5) in NAc MSNs limits the formation of reward-cue associations in rodent models of drug seeking, but not sucrose seeking, leading to decreased relapse-like behavior. However, whether HDAC5 reduces drug seeking behavior through its own deacetylase activity or through the recruitment of co-repressors is unknown. Furthermore, these …

Living With Alzheimer’S: A Guide To How To Lower The Risk Of Memory Loss & Care For Those With Alzheimer’S, Mona Muzammil, Washain Muzammil

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Despite the frequent characterization of Alzheimer's disease as a “loss of self,"" this enlightening book demonstrates unequivocally that a person's unique self persists throughout the course of the disease. The important message in Caring for People with Alzheimer’s is how much can be done in care settings to support a person's sense of identity and thereby enrich the lives of people experiencing the many losses associated with dementia. Drawing from a diverse body of research, this book brings together the recommendations of the best thinkers and practitioners in multiple disciplines to illustrate the meaning of self and the importance of …

Life On The Dry Side: A Roadmap To Understanding Desiccation Tolerance And Accelerating Translational Applications, R A Marks, J T B Ekwealor, M A S Artur, L Bondi, T C Boothby, O M S Carmo, D C Centeno, K K Coe, H J W Dace, S Field, A Hutt, S Porembski, A Thalhammer, L Van Der Pas, A J Wood, P Alpert, D Bartels, S Boeynaems, M N Datar, T Giese, W I Seidou, S M Kirchner, J Köhler, U G V S S Kumara, J Kyung, R Lyall, B D Mishler, J B V T Ndongmo, M S Otegui, V Reddy, J Rexroth, S M Tebele, R Vanburen, J Verdier, U C Vothknecht, M F Wittenberg, E Zokov, M J Oliver, S Y Rhee

Duncan NRI Faculty and Staff Publications

To thrive in extreme conditions, organisms have evolved a diverse arsenal of adaptations that confer resilience. These species, their traits, and the mechanisms underlying them comprise a valuable resource that can be mined for numerous conceptual insights and applied objectives. One of the most dramatic adaptations to water limitation is desiccation tolerance. Understanding the mechanisms underlying desiccation tolerance has important potential implications for medicine, biotechnology, agriculture, and conservation. However, progress has been hindered by a lack of standardization across sub-disciplines, complicating the integration of data and slowing the translation of basic discoveries into practical applications. Here, we synthesize current knowledge …

Enhancing State-Of-The-Art Motor Imagery Classification With Reinforcement Learning, Anton Shepelev

USF Tampa Graduate Theses and Dissertations

One of the key obstacles to the rapid adoption of non-invasive Brain-Computer Interfaces (BCIs) for Motor Imagery (MI) is the low signal-to-noise ratio, and the substantial data requirements which can be mentally taxing for users. EEGNet, a compact Convolutional Neural Network (CNN), has long been considered the state-of-the-art (SOTA) for MI classification, demonstrating strong performance even with limited data. However, recent studies advocate for integrating Deep Reinforcement Learning (RL) to further enhance classification accuracy by dynamically optimizing feature extraction and decision-making processes. Despite this potential, practical implementations remain scarce due to challenges in stabilizing RL training and adapting it to …

A Long Non-Coding Erna Forms R-Loops To Shape Emotional Experience-Induced Behavioral Adaptations, Rose Marie Akiki

MUSC Theses and Dissertations

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as Npas4. We discovered that a conserved, long non-coding enhancer RNA (lnc-eRNA) transcribed from an activity-sensitive enhancer produces DNA-RNA hybrid R-loop structures that support 3D chromatin-looping of the enhancer and proximal promoter and stimulus-induced, rapid Npas4 gene induction. We also show that this Npas4 lnceRNA and its R-loops are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, …

Clinical And Imaging Correlates Of Cognitive Impairment Patterns In Early Unilateral Brain Injury Associated With Sturge-Weber Syndrome, Halah Keramane, Csaba Juhasz Md, Phd, Michael E. Behen Phd, Aimee Luat Md

Medical Student Research Symposium

Background: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disease characterized by cerebral venous malformations leading to early damage of affected brain regions. Clinical symptoms include seizures, motor and cognitive impairment. Most SWS patients have unilateral brain involvement, and previous studies reveal substantial neurological plasticity in some of them. Some children with left-hemispheric damage demonstrate, paradoxically, preserved verbal functions and reduced nonverbal functions (a “crowding” effect), suggesting contralateral functional reorganization from damaged cortical regions. We evaluated the incidence as well as clinical and imaging correlates of such functional reorganization/crowding.

Methods: Forty-six patients (age: 2.5-24 years) with unilateral SWS underwent neurocognitive evaluations …

Assessing Platelet Counts As Predictors Of Vasospasm And Discharge Outcomes In Aneurysmal Subarachnoid Hemorrhage, Alexander Weiss M.S., B.S., B.A., Jared C. Reese M.D., Pouya Entezami M.D., M.S.

Medical Student Research Symposium

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) carries a 21.9% 30-day case fatality rate, largely due to complications from cerebral vasospasm (CVS), which can lead to delayed cerebral ischemia (DCI). Despite extensive research, the best predictive biomarkers for vasospasm remain unclear. This study evaluates whether variations in platelet count predict vasospasm and patient outcomes in aSAH.

Methods: A retrospective cohort study included 297 aSAH patients from the Henry Ford Health System electronic medical records. Inclusion criteria required an aSAH diagnosis, hospital admission within 24–48 hours of symptom onset, transcranial Doppler (TCD) data, daily platelet count, and modified Rankin scale (mRS) …

Breaking The Synaptic Vesicle Cycle: Mechanistic Insights Into Presynaptic Dysfunctions In Epilepsy, Kevin Jiang, Lu-Tang Yang, Mingshan Xue

Duncan NRI Faculty and Staff Publications

Synaptic dysfunction is a hallmark of many neurological disorders including epilepsy. An increasing number of epilepsy-causing pathogenic variants are being identified in genes encoding presynaptic proteins that affect every step of the synaptic vesicle cycle, from vesicle loading, tethering, docking, priming, calcium sensing, fusing, to recycling. These different molecular dysfunctions result in converging impairment of presynaptic neurotransmitter release, yet lead to diverse epileptic disorders. This review focuses on representative monogenic epileptic disorders caused by pathogenic variants of key presynaptic proteins involved in different stages of the synaptic vesicle cycle: SYN1 (vesicle pool regulation), STXBP1 (vesicle docking, priming, and fusion), and …

De Novo Variants In Cdkl1 And Cdkl2 Are Associated With Neurodevelopmental Symptoms, Ali H Bereshneh, Jonathan C Andrews, Daniel F Eberl, Guney Bademci, Nicholas A Borja, Stephanie Bivona, Wendy K Chung, Shinya Yamamoto, Michael F Wangler, Shane Mckee, Mustafa Tekin, Hugo J Bellen, Oguz Kanca

Duncan NRI Faculty and Staff Publications

The CDKL (cyclin-dependent kinase-like) family consists of five members in humans, CDKL1-5, that encode serine-threonine kinases. The only member that has been associated with a Mendelian disorder is CDKL5, and variants in CDKL5 cause developmental and epileptic encephalopathy type 2 (DEE2). Here, we study four de novo variants in CDKL2 identified in five individuals, including three unrelated probands and monozygotic twins. These individuals present with overlapping symptoms, including global developmental delay, intellectual disability, childhood-onset epilepsy, dyspraxia, and speech deficits. We also identified two individuals with de novo missense variants in CDKL1 in the published Deciphering Developmental Disorders (DDD) and GeneDx …

Proposed Method For Analyzing Cognitive Effects Of Chiari Malformation Type I And The Progression Following Cerebral Tonsil Reduction, Isabella Gleason

Selected Honors Theses

Chiari Malformation Type I (CM-I) is a neurological condition characterized by the descent of cerebellar structures through the foramen magnum. This malformation can be associated with cognitive implications, including impaired executive functioning, slowed processing speed, memory deficits, difficulties with attention and concentration, irregularities in emotional processing, and challenges in communication and fluency. Research indicates that cognitive dysfunction is prevalent in CM-I patients, affecting their daily lives. There are two surgical treatments commonly recommended for CM-I: posterior fossa decompression (PFD) and cerebral tonsil reduction (CTR). While both interventions are supported in the literature, studies on their long-term effects and effectiveness remain …

Interactions Between Explicit And Implicit Memories During Sensorimotor Adaptation And After Concussion, Devon Lantagne

Dissertations (1934 -)

Sensorimotor adaptation is a form of motor learning whereby a motor skill is adjusted in the face of a disturbance to return performance to desired performance. This process uses memories of previous experiences to guide future movements. While the temporal characteristics of adaptation have been well studied, the extent to which these memories are explicit, implicit, or a mixture of both is unclear. In this Dissertation, I conduct three studies to investigate the relative contributions of sensorimotor memories when adapting to stochastic spring-like loads applied to the hand. By implementing computational modeling and system identification techniques, I fit memory models …

Glucose Uptake In Pigment Glia Suppresses Tau-Induced Inflammation And Photoreceptor Degeneration, Mikiko Oka, Sho Nakajima, Emiko Suzuki, Shinya Yamamoto, Kanae Ando

Duncan NRI Faculty and Staff Publications

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures …

De Novo Variants In Rybp Are Associated With A Severe Neurodevelopmental Disorder And Congenital Anomalies, Monika Weisz-Hubshman, Lindsay C Burrage, Sharayu V Jangam, Jill A Rosenfeld, Sandra Von Hardenberg, Anke Bergmann, Manuela Friederike Richter, Malgorzata Rydzanicz, Rafal Ploski, Agnieszka Stembalska, Wendy K Chung, Rebecca R Hernan, Foong Y Lim, Theresa Brunet, Steffen Syrbe, Boris Keren, Solveig Heide, David R Murdock, Hongzheng Dai, Fan Xia, Shamika Ketkar, Brian Dawson, Vinodh Narayanan, Hillary K Graves, Undiagnosed Diseases Network, Michael F Wangler, Carlos Bacino, Brendan Lee

Duncan NRI Faculty and Staff Publications

Purpose: Polycomb group proteins are key epigenetic transcriptional regulators. Multiple neurodevelopmental disorders are associated with pathogenic variants of the genes encoding Polycomb group proteins. RYBP is a core component of the noncanonical Polycomb Repressor Complex 1; however, its role in disease is unclear.

Methods: Functional consequences of RYBP variants were assessed using in vitro cellular and in vivo Drosophila melanogaster studies.

Results: We described 7 individuals with heterozygous de novo variants of RYBP and their clinical findings, including severe developmental delay, dysmorphisms, and multiple congenital anomalies. We showed that all single-nucleotide variants in RYBP localize to the N-terminal domain of …

Alpha-Synuclein Phosphomimetic Y39e And S129d Knock-In Mice Show Cytosolic Alpha-Synuclein Localization Without Developing Neurodegeneration Or Motor Deficits, Youngdoo Kim, Bhupesh Vaidya, Joseph Mcinnes, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-synuclein (α-Syn) in Lewy bodies and Lewy neurites. Phosphorylation of α-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of α-Syn phosphorylation in synucleinopathy, we generated two Snca knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 (Snca^Y39E or Snca^S129D) which manipulated epitopes phosphorylated in the PD brain. Both Snca^Y39E and Snca^S129D KI mice displayed increased α-Syn phosphorylation, enhanced …