Molecular and Cellular Neuroscience Commons^™

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

The Cardinal Edge

No abstract provided.

Situation Mouse All Floxed Up: Exploring Phenotypic Abnormalities In Bdnf Floxed Mice, Marissa A. Burkman

All NMU Master's Theses

Animal research is a contentious topic in both the scientific and general communities.  It is essential that our animal models accurately and predictably depict intended phenotypes, necessitating careful colony monitoring and maintenance.  Volunteer animal staff in the Ottem Laboratory became concerned when mice with LoxP sites flanking the BDNF gene depicted anxiety-like behaviors such as aggression, difficulty handling, and increased agitation.  Though many studies have noted behavioral and phenotypic abnormalities related to large gene inserts, few have noted abnormalities with small gene inserts such as the 34 bp LoxP site.  Brandt (2018) performed a three-stage behavioral protocol on these mice …

Obesity Does Not Significantly Impact Clinical Outcomes Following Anterior Cervical Discectomy And Fusion, Ishan Shah, Alejandro Perez-Albela, Riya Shah, Charles Furlong, Puru Sadh, John Czerwein, Alan Daniels, Bryce A Basques

SKMC Student Presentations and Publications

BACKGROUND: With obesity rates rising among patients undergoing anterior cervical discectomy and fusion (ACDF) and more procedures shifting to outpatient settings, this study aimed to evaluate the impact of body mass index (BMI) on complications, sagittal alignment, and patient-reported outcomes (PROs).

METHODS: A prospectively maintained database of 302 patients who underwent ACDF for myelopathy or radiculopathy between 2020 and 2022 at a single academic center was analyzed. Patients were stratified into four BMI categories: normal (18.5-< 25), overweight (25-< 30), obese class I (30-< 35), and obese class II/III (≥35). Collected data included demographics, comorbidities, perioperative variables, radiographic measures (cSVA, Cobb angle, etc.), and PROs (VAS, NDI). Univariate regression compared demographics, alignment, and PROs, while multivariate analyses assessed complications and perioperative factors.

RESULTS: BMI was not independently associated with higher rates of postoperative complications, including adjacent segment disease, subsidence, reoperation, or other adverse events. Patients in …

Local Angiotensin Converting Enzyme 2 (Ace2) Enzymatic Activity Modulates Cholinergic Interneuron Function In The Dorsolateral Striatum, Aria R. Walls

Dissertations, Theses, and Capstone Projects

The renin angiotensin system (RAS) is an ancestrally ancient peptidergic signaling pathway best known for its role regulating blood pressure in the periphery. However, its presence and importance in the central nervous system has more recently been identified and is less well understood. Previous work shows RAS is expressed in the nigrostriatal pathway of the basal ganglia and has been implicated in basal ganglia disorders including Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). Interestingly, the canonical and noncanonical arms of the RAS pathway produce opposite effects on PD disease vulnerability and progression. The shift from the neurodegenerative canonical RAS to …

Silver Nanoparticle-Induced Disruption Of Astrocytic Morphology And Synaptic Microarchitecture In Rat Brain, Elli Williams

Theses, Dissertations and Capstones

Silver nanoparticles (AgNPs) are widely incorporated into consumer and medical products due to their antibacterial properties, increasing the potential for chronic exposure. AgNPs can be released into the environment, enter the body through ingestion or inhalation, cross the blood-brain barrier (BBB), and bioaccumulate in brain tissue. Previous in vitro studies demonstrate that AgNP exposure disrupts cytoskeletal organization and induces neurite collapse in neural cells, suggesting vulnerability of cytoskeleton-dependent structures in vivo. Astrocytes, through their perisynaptic astrocytic processes (PAPs) and perivascular endfeet, play critical roles in maintaining synaptic and neurovascular architecture, both of which rely heavily on cytoskeletal integrity. This …

Rna-Sequence-Driven Identification Of Differentially Expressed Genes In Α-Crystallin-Deficient Zebrafish, Kehlie Hopper

SPARK Symposium Presentations

Fetal Alcohol Syndrome (FAS) is a condition that develops in infants when exposed to alcohol in utero, leading to physical impairments such as reduced eye size and disrupted retinal function. Alpha-crystallin A is a key structural protein required for proper lens development and maintenance of transparency, while Alpha-crystallin B plays a protective role against cellular stress during eye development. In this study, I compared AB wild-type (ABWT), αA-crystallin knockout (cryaa), and αB-crystallin knockout (cryaba) zebrafish to investigate how the loss of these proteins influences eye development under ethanol exposure. The cryaa mutants exhibited reduced eye size even under control conditions, …

Metabolism As A Regulator Of Sleep And Cortical Activity In Health And Alzheimer’S Disease, Nicholas J. Constantino

Theses and Dissertations--Neuroscience

Metabolic flexibility is essential for maintaining normal physiological function, enabling an organism to sense, flux, utilize, and switch fuel sources in response to changing energetic availability, demand, and cellular needs. Energetic demands are state-dependent, with wake and sleep exhibiting distinct metabolic profiles. Sleep is highly sensitive to changes in metabolism and requires metabolic flexibility to both transition into and maintain sleep stability. Alzheimer’s disease (AD) is increasingly recognized as a disease of altered metabolism yet is often framed as a disease of energetic failure. We instead define AD as a disease of metabolic inflexibility, characterized not by insufficient energy availability, …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

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 …

Microglial Apoe Across Alzheimer’S Disease-Relevant Pathologies, Georgia Nolt

Theses and Dissertations--Physiology

APOE exists as three common alleles (APOE2, APOE3, APOE4) that encode their corresponding protein isoforms (apoE2, apoE3, apoE4). Despite differing by only one or two single-amino acid substitutions, each APOE allele confers a distinct AD risk profile with APOE4 increasing risk by 28% and APOE2 decreasing risk by 14% compared to the most commonly expressed APOE3 allele. While traditionally considered “neutral,” APOE3 still accounts for ~36% of AD cases while APOE4 contributes ~57%, indicating that the majority of AD cases would not occur in the absence of the APOE3 and APOE4 alleles. Microglia, the resident phagocytic immune cells …

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 …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

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 Serotonin 1b Receptor In Psilocybin’S Therapeutic-Like Mechanisms: From Behavior To Network Reorganization, Sixtine Fleury

Dartmouth College Ph.D Dissertations

Mood disorders represent a substantial and growing global health crisis, with ~10 million adults in the US meeting criteria for a major depressive disorder (MDD). Current first-line treatments such as SSRIs require long-term daily administration and fail a significant proportion of patients, driving renewed interest in rapid-acting alternatives. Psilocybin, a serotonergic psychedelic, shows growing clinical evidence of efficacy in treating depressive and anxiety disorders, often producing therapeutic effects persisting weeks to months following a single dose. Yet, the neural mechanisms underlying these enduring effects remain poorly understood and have been largely attributed to the serotonin 2A receptor (5-HT2AR) based on …

Forcing A Molecule To Switch: Quantifying Mechanical Control At The Atomic Scale, A. M. Shashika D. Wijerathna, Markus Zirnheld, Michael L. Hildebrand, Myles Perry, Marjorie Cenese, Yuan Zhang

Physics Faculty Publications

Mechanically induced conformational switching at the single-molecule level represents a fundamental mechanism for molecular functionality, yet quantitative characterization of the underlying force and energy landscape remains limited. Here, we study individual TBrPP-Co(II) molecules on Au(111) using qPlus atomic force microscopy. By reconstructing interaction potentials from 3D Δf(x,y,z) data, we determine a threshold force of ∼96 ± 8 pN and a tip-induced switching interaction energy of ∼38 ± 4 meV associate with the conformational transition. The isolated tip-molecule force follows a power law (exponent ∼6), indicating dominance of long-range van der Waals interactions. …

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Investigation Of Mono-Allelic Rack1 Deletion Effects On Cell Growth And Pkc Mrna Expression, Ashen Quiambao

Seton Hall University Dissertations and Theses (ETDs)

The µ-opioid receptor is a primary target of clinically used opioids, and RACK1 regulates its transcription by physically interacting with MOR transcription regulator PCBP1 in the cytosol to prevent its nucleus translocation. Two mono-allelic RACK1 knockout cell lines named RACKA and RACKB were generated by the CRISPR-Cas9 technique using WT NMB neuroblastoma cells. As RACK1 also contains a PKC-binding domain, this study aims to evaluate the impacts of mono-allelic deletion on cell growth rates and PKC isoform expression. Although a slight decreased tendency of growth rate in RACKA and RACKB cells was observed when compared to that of WT NMB …

Stress During Adolescence: A Characterization Of Anxiety-Like Behavior, And The Mrna Expression Of Neuroimmune Factors, Clock And Stress Genes In Corticolimbic Areas., Annette Fernandez Oropeza, Annette K. Fernandez Oropeza

Biomedical Sciences ETDs

Adolescence represents a critical window of frontal cortex (FC) maturation and corticolimbic circuit refinement that supports stress and emotion regulation. Disruption of these processes by early-life insults such as prenatal alcohol exposure (PAE) or adolescent stress increases vulnerability to anxiety and mood disorders, in part through circadian–immune dysregulation. The circadian transcription factor Bmal1 and the proinflammatory cytokine tumor necrosis factor-alpha (TNFα) have emerged as key regulators of neuroimmune signaling and synaptic communication, yet their interactions across developmental risk contexts remain poorly understood. This dissertation examined the effects of mild adolescent isolation stress, with and without PAE, on anxiety-like behaviors and …

Generating Predictive Gene Expression Signatures For Alzheimer's Disease Using Postmortem Brain Tissue, Ashley Duche

Pharmaceutical Sciences (PhD) Dissertations

Background: Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ) plaques and tau protein aggregates. These pathological features develop in specific brain regions, but why some areas are more vulnerable to early AD-related changes remains unclear. To address this, predictive gene expression signatures were developed to explore the molecular mechanisms underlying regional susceptibility to AD pathology.

Methods: This was performed using postmortem brain (PMB) tissue from participants in the Religious Orders Study and Memory and Aging Project (ROSMAP), Mayo Clinic, and Mount Sinai Brain Bank (MSBB) to generate gene expression signatures from six brain …

Capsinoids, Non-Pungent Trpv1 Agonists, Induce A Mild Hypothermia That Provides Short- And Long-Term Neuroprotection After Ischemic Stroke, Alexander Andersohn, Alexander Andersohn

Dissertations and Theses (Open Access)

Therapeutic hypothermia (TH) has demonstrated neuroprotection in instances of cardiac arrest and neonatal hypoxia/ischemia but faces different challenges in application to stroke due to the activation of cold defense mechanisms in conscious patients. This dissertation examines the efficacy and specificity of capsinoids (a purified mixture of capsiate and dihydrocapsiate) to induce a sustained mild hypothermia in conscious mice that is neuroprotective after stroke. Capsinoids function as TRPV1 agonists. However, unlike capsaicin, capsinoids are vulnerable to esterase-mediated breakdown, thus significantly restricting their action to the site of delivery. We showed that capsinoids delivered intraperitoneally (IP) to mice induced a TRPV1-dependent drop …