Molecular and Cellular Neuroscience Commons^™

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

The Rpm-1/Phr Signaling Hub Modulates Tau-Induced Neurodegeneration Through Regulation Of Microtubule Stability And Mapk Pathways In C. Elegans, Xinxing Ding

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia, are characterized by the accumulation of pathological tau proteins and progressive neuronal loss. Although research regarding tau-mediated toxicity is extensive, the specific pathology that determine whether neurons maintain homeostasis or succumb to collapse under tau-induced stress remain incompletely elucidated. A central, yet still insufficiently understood, feature of these diseases is the disruption of the microtubule (MT) cytoskeleton . The PHR protein family is evolutionarily highly conserved; within this family, RPM-1 in C. elegans functions as an intracellular signaling hub that regulates axon development, synapse formation, axon termination, and various microtubule-associated processes. This …

Survivin And Caspases Coordinate Proteolytic Cleavage Of The Saga Chromatin Modifying Complex, Elinor Harrison, Alejandro Damian, Cj Talton

Medical Student Research Symposium

Title: Survivin and Caspases Coordinate Proteolytic Cleavage of the SAGA Chromatin Modifying Complex

Elinor Harrison¹, Alejandro Damian¹, CJ Talton¹, Jelly H Soffers¹, Abudu I Bello¹, Kara M Costanzo¹, Joe Bean¹, Ryan D Mohan¹

¹Wayne State University School of Medicine

Background: The Spt Ada Gcn5 Acetyltransferase (SAGA) chromatin modifying complex is a critical regulator of gene expression. Mutation or stoichiometric imbalance of SAGA subunits leads to a spectrum of diseases in model organisms and in humans, including neurodegeneration. SAGA contributes to gene activation through coordinated …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

The Sonic Hedgehog Effector Smoothened Modulates Cholinergic Interneuron Activity, Physiology, And Striatum-Dependent Behaviors, Santiago Uribe-Cano

Dissertations, Theses, and Capstone Projects

The striatum is a central node in action selection and associative learning, integrating cortical, thalamic, and neuromodulatory input. Among its principal modulators, dopamine (DA) and acetylcholine (ACh) are known for their temporally coordinated yet mechanistically distinct influences on striatal output. However, the upstream signals that regulate their dynamic interplay, particularly within cholinergic interneurons (CINs)—the primary source of striatal ACh—remain incompletely characterized. This dissertation investigates the role of Smoothened (Smo), a G protein-coupled receptor (GPCR) effector of Sonic Hedgehog (Shh) signaling, in modulating ACh signaling dynamics in the striatum.

Building on evidence that midbrain DA neurons co-release Shh and that CINs …

Mechanistic Insights Into The Neuroprotective Effects Of The Antidepressant Agomelatine In Alzheimer's Disease, Grace Terry

Dissertations, Theses, and Capstone Projects

Alzheimer’s Disease (AD) is a complex neurodegenerative disease that has limited treatment options and no cure. AD is characterized by robust pathology including extracellular amyloid beta plaques, intracellular neurofibrillary tangles, neuronal and synaptic loss, neuroinflammation, and brain atrophy. AD presents with cognitive decline and memory loss but only years after neuropathology has started to accumulate. This robust pathology has made AD difficult to treat and highlights the need for therapeutics that modulate multiple pathways. Agomelatine (AGO) was selected by a high-throughput machine learning drug repurposing algorithm by our collaborator Dr. Lie Xie (Hunter College Dept. of Comp. Sci.) as having …

Advanced Interactions Of Directed Energy With Retinal Pigment Epithelial Cells And Their Photochemical And Photothermal Responses, Jin B. Ha

Theses & Dissertations

Excess optical radiation can injure the retina through either rapid heat deposition (photothermal damage) or cumulative photo‑oxidative stress (photochemical damage), yet current laser‑safety limits treat these mechanisms as independent. To test that assumption, this dissertation integrated systematic wavelength, duration and temperature‑controlled laser exposures with live/dead fluorescence imaging in a melanin‑loaded hTERT‑RPE1 monolayer model. First, concurrent 447 nm (blue) and 2 µm (infra‑red) beams delivered for 200 s demonstrated a strong thermal–photochemical synergy: each beam alone was sub‑threshold (≤25 % lethality) but together produced 100 % RPE death without exceeding 50 °C, proving that modest heating markedly lowers the photon dose …

The Role Of Androgen Receptor And B2/Alu Sine Rna Interaction In Hippocampal Dendritic Development, Troy A. Richter

Graduate Doctoral Dissertations

Once dismissed as “junk”, transposable elements have recently gained recognition for their regulatory roles, especially in the brain. During development, circulating androgens promote proper morphological development of hippocampal neurons. We and others have shown that murine B2 SINE RNA is a regulator in the rodent hippocampus. It is unknown, however, if B2 is necessary for the proper development of hippocampal neurons. This dissertation investigates the role of murine B2 in the development of primary hippocampal neurons in combination with androgen treatment. We first examined the role of ALU SINE and androgen receptor in a prostate cancer cell model and found …

Investigating The Capacity Of Tdp-43 Low Complexity Domain To Target Protein Aggregates In Yeast, Nicholas J. Grahame

Biology Summer Fellows

Utilizing protein TDP-43 and fluorescent proteins to:

Investigate TDP-43’s LCD region in protein aggregates. Use fluorescent protein tagging to visualize co-localization and aggregation. Leverage yeast as a model system for studying LLPS and aggregation.

Can we target chaperone proteins to TDP-43 LCD region?

Topodino: Self-Supervised Topological Representation Learning For Neuronal Morphologies, Yasser Binbisher

Master's Theses

Neuronal cell types are categorized by transcriptomic identity, yet their morphological heterogeneity defies this classification. In response, researchers have adopted unsupervised graph representation learning as a tool to reveal morphological variation within single-class transcriptomic types. However, the complex geometry of neuronal morphology—especially long axons and dense dendrites—challenges graph neural networks, which struggle with message propagation across extended structures. To mitigate this, current approaches enforce sub-sampling on neuronal graphs and omit axons entirely, sacrificing critical biological features for computational efficiency. To overcome this trade-off, this thesis introduces TopoDINO, a self-supervised, topology-aware representation learning model designed to preserve the full hierarchical organization …

Peripheral Neuroimmune Mechanisms Of Chronic Back Pain, Aleyah Esther Goins

Biomedical Sciences ETDs

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological …

Mitochondrial Network Expansion And Loss During Oligodendrocyte Life And Death, Xhoela Bame

Dartmouth College Ph.D Dissertations

Oligodendrocytes are the myelinating cells of the central nervous system, known for modulating signal transmission, refining neural circuits, and providing metabolic support to axons. Oligodendrocytes are generated throughout life from oligodendrocyte precursor cells (OPCs) and are damaged or lost in demyelinating and neurodegenerative diseases and age-related pathologies. Thus, understanding the cellular checkpoints that occur during the generation and degeneration of oligodendrocytes is crucial for maintaining their population in health and recovering it in disease and aging.

Using high-resolution optical imaging, I have discovered a dynamic redistribution and subcellular partitioning of mitochondria during oligodendrogenesis. Mitochondria transiently expanded towards the differentiating OPC …

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …

Neuronal Cftr: A Study Of Subcellular Localization And Interactions With Implications For A Role In Synaptic Transmission, Brandon J. Leviskas

LSU Doctoral Dissertations

Protein-protein interactions vary among cell types and the localization of these interactions help to define protein function. The function of cystic fibrosis transmembrane conductance regulator (CFTR) is well established in the context of epithelial tissue due to the debilitating effects of its mutations that cause the disease cystic fibrosis. While in neurons a role has been established in our lab for CFTR in the regulation of cytosolic Cl- in retinal amacrine cells (ACs). This research sets out to learn if CFTR has a synaptic role. Exploring this potential role, localization of CFTR was examined using fluorescent and immunogold labeled transmission …

Comprehensive Sumo Proteomic Analyses Identify Hiv Latency-Associated Proteins In Microglia., Fergan Imbert, Dianne Langford

Rowan-Virtua School of Osteopathic Medicine Departmental Research

SUMOylation, the post-translational modification of proteins by small ubiquitin-like modifiers, plays a critical role in regulating various cellular processes, including innate immunity. This modification is essential for modulating immune responses and influencing signaling pathways that govern the activation and function of immune cells. Recent studies suggest that SUMOylation also contributes to the pathophysiology of central nervous system (CNS) viral infections, where it contributes to the host response and viral replication dynamics. Here, we explore the multifaceted role of SUMOylation in innate immune signaling and its implications for viral infections within the CNS. Notably, we present novel proteomic analyses aimed at …

Loss Of Lgl1 Increases Expression Of C-Jun And Dcx In The Svz And Rms Of The Mouse Brain, Madison Leigh Gutierrez

Cal Poly Humboldt theses and projects

Glioblastoma (GBM), the most aggressive and treatment-resistant subtype of glioma, accounts for the majority of brain tumor–related mortality. A defining feature of GBM is its ability to invade healthy brain tissue through extensive cell migration, which severely limits the effectiveness of surgical and pharmacological treatments. Increasing evidence suggests that GBM cells activate gene programs known to drive normal neural stem and progenitor cell (NSPC) migration; however, the precise molecular mechanisms shared between NSPCs and GBM cells remain poorly understood. Lethal (2) giant larvae 1 (Lgl1), a conserved cortical cytoskeletal protein, has emerged as a key regulator of polarity and migration. …

Cgrp Modulation Of Intracellular Calcium Levels In Trigeminal Ganglion Neurons And Glia, Nicole M. Nalley

Graduate Theses/Dissertations

Elevated levels of calcitonin gene-related peptide (CGRP) are implicated in migraine and TMD pathology, but its effects on the excitability state of Aδ and C-fiber neurons and glia have not been investigated. The goal of this study was to determine changes mediated by CGRP on intracellular calcium levels in trigeminal ganglion neurons and glia in response to depolarizing stimulation. Intracellular calcium levels were determined in Aδ and C-fiber neurons of primary trigeminal ganglion cultures obtained from neonatal Sprague Dawley rats using Fura-2 and fluorescent microscopy. Cells were left untreated or preincubated for 2 hours with CGRP, then incubated with the …

Inductions Of Long-Term Potentiation With Biomimetic Electromagnetic Fields In Primary Neurons, Cooper E. Kansala

Theses and Dissertations (Comprehensive)

Endogenous brain rhythms guide neural communication and plasticity, raising the question of whether weak, temporally structured electromagnetic fields (EMFs) that mimic these rhythms can modulate neuronal activity in a targeted, biomimetic manner. This thesis investigates whether patterned EMFs designed to reflect the temporal structure of hippocampal long-term potentiation (LTP) are more effective at inducing neural plasticity than conventional sinusoidal fields or no stimulation at all. Cortical neurons cultured from postnatal rats were exposed to patterned EMFs for 30 minutes and assessed across three distinct experimental domains. In Chapter 2, microelectrode array (MEA) recordings revealed that the LTP-patterned field significantly increased …

Regulation And Function Of Mec-2 Alternative Splicing In Single Cells, Canyon Calovich-Benne

Biological Sciences Theses and Dissertations

One mechanism for generating diversity at the single cell level is selective expression of a unique set of transcription factors (TFs) and RNA binding proteins (RBPs). These regulatory factors contribute to functions of cells by controlling cell fate, turning genes on and off, and processing of transcripts either co- or post-transcriptionally. Many genes, especially neuronal genes, have multiple different splicing events, promoters, and/or polyadenylation sites. Post-transcriptional coordination is in the infancy of being studied and the functional consequences of this coupling at the single cell level has yet to be explored. Here we show, mec-2 coordination of alternative transcription start …

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Microglial Dynamics And Mechanisms Underlying The Phagocytosis Of Dying Oligodendrocytes, Genaro E. Olveda

Dartmouth College Ph.D Dissertations

Myelin is a complex multilamellar structure, generated by oligodendrocytes, that ensheaths axons and is a vital component for neural processing. Degeneration of both oligodendrocytes and their myelin sheaths is a common pathological feature associated with aging and neurodegenerative diseases. Efficient removal of the cellular and myelin debris is crucial for remyelination and prevention of further degeneration. Microglia, the primary phagocytes of the CNS, are thought to play a key role in this process. To investigate the cellular dynamics underlying microglia-mediated clearance of degenerating oligodendrocytes and myelin sheaths, at the single cell level, we developed a novel model for inducible cortical …

Development Of Vasculature Patterns In A Mouse Model Of Supratentorial Ependymoma, Jackson Ayers

Honors Scholar Theses

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …