Molecular and Cellular Neuroscience Commons^™

Microglia Polarize In Response To Transactive Response Dna-Binding Protein-43 (Tdp-43) And Display Partial Recovery After Removal Of The Stimulus, Alicen Wilcox

Honors Theses

The proper response to protein signals is necessary for a healthy central nervous system (CNS), and protein dysregulation is a feature of neurodegenerative diseases. Transactive response DNA-binding protein-43 (TDP-43) is an intranuclear protein, but mislocalization is associated with amyotrophic lateral sclerosis (ALS). TDP-43 is released into the extracellular space where it is sensed by microglia, the CNS-resident immune cells. Our data and the literature suggest that microglia respond to TDP-43 dysregulation by increasing CNS inflammation. The goal of this study was to determine the impact of TDP-43 on microglial function and the extent to which microglia recovery. To study the …

The Functional And Structural Consequences Of Aberrant Microglial Activity In Major Depressive Disorder, Jasmine D. Cakmak

Electronic Thesis and Dissertation Repository

Major depressive disorder (MDD) is a highly debilitating neuropsychiatric illness which has been linked with increases in both peripheral and central inflammation, as well as with changes in connectivity. Although countless studies have investigated these two topics, the relationship between neuroinflammation and functional/structural connectivity has not been explored. Using [¹⁸F]FEPPA PET imaging, we measured translocator protein-related (TSPO) microglial activity in the subgenual anterior cingulate cortex (sgACC) and insula and confirmed significantly increased [¹⁸F]FEPPA uptake in depressed patients (N=12) compared to healthy controls (N=23). Using a seed-based ROI analysis of fMRI data, we found that patients show …

Investigation Of Notch Signaling In Cone Fate Specification In Vertebrate Retina, Xueqing Chen

Dissertations, Theses, and Capstone Projects

In the vertebrate retina, cone photoreceptors are crucial for high acuity color vision. Several retinal diseases lead to loss of cones and there is a need to identify the normal developmental genesis of these cells to inform the development of stem cell-based therapies. Cone genesis has previously been shown to be repressed by Notch signaling, however, the mechanism by which Notch signaling controls cone fate determination is still unclear. It has been identified that cone photoreceptors are formed from multipotent retinal progenitor cells (RPCs) that first generate genetically-defined, restricted RPCs with limited mitotic and fate potential to preferentially form cones …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Examining The Role Of Chloride Homeostasis And Pge2 Signaling In The Neuroendocrine Stress Response To Inflammation, Samuel A. Mestern

Electronic Thesis and Dissertation Repository

The brain senses inflammatory signals and drives the release of glucocorticoids (GCs) — potent immunosuppressants — via the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This inflammation-induced HPA axis activation is largely mediated by prostaglandin E2 (PGE2), acting on two subtypes of the PGE2 receptor, EP1 and EP3. Recently, our group revealed EP3 signaling mechanisms that excite HPA axis regulatory neurons. This thesis sought to tease out the remaining EP1 signaling mechanisms. Considering that the excitability of HPA axis regulatory neurons is constrained by GABA_A receptor-mediated synaptic inhibition that relies on low-level intracellular Cl^-. We hypothesized that PGE2-EP1 …

Investigating The Effects Of Maternal Immune Activation On Sensory Processing: Timing, Immune Mechanisms, And Gene-Environment Interactions, Faraj Haddad

Electronic Thesis and Dissertation Repository

Maternal infection during the first or second trimester of pregnancy poses a risk factor for the child to have neurodevelopmental disorders like autism spectrum disorder (ASD) and schizophrenia. Various clinical and preclinical studies have shown that the maternal immune response to infection, also known as maternal immune activation (MIA), can disrupt fetal brain development.

Over the past two decades, MIA has been studied in rodents using the Polyinosinic Polycytidylic acid (Poly I:C) rodent model. Poly I:C has a molecular pattern resembling viruses that can induce a robust immune response. Following exposure to Poly I:C MIA, rodent offspring exhibit many brain …

Effects Of Palmitate On The Expression Of Inflammatory Cytokines In Microglial Cells, Shiyu Ma

Seton Hall University Dissertations and Theses (ETDs)

Obesity has become a pandemic health issue for the development of more serious illnesses such as insulin resistance, cardiovascular diseases, and hypertension. Among those pathological conditions, low grade chronic inflammation triggered by saturated fatty acids (SFA) such as palmitate (PA) has been suggested to be the culprit of crimes and various signaling modulators ranging from cellular surface receptors such as toll like receptors (TLRs) and G- protein – coupled receptor 40 (GPR40) to intracellular kinases like mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) have been postulated. In this study, mouse BV2 cells were treated with different concentrations of …

Investigation Of The Hsp90 Co-Chaperone, Sti1, In Cellular Resilience And Neurodegenerative Diseases, Rachel E. Lackie

Electronic Thesis and Dissertation Repository

In neurodegenerative diseases, certain proteins misfold and form toxic aggregates that cause brain matter atrophy, leading to decline in motor and/or cognitive functions. To maintain cellular proteostasis and survival, molecular chaperones regulate protein maturation and help to prevent aberrant protein aggregation. The molecular chaperone Hsp90 regulates hundreds of proteins and interestingly, several of those are misfolded in neurodegenerative diseases. Stress inducible-phosphoprotein-1 (STI1, STIP1), an Hsp90 co-chaperone, orchestrates client protein transfer between chaperones Hsp70 and Hsp90 through physical interactions with both chaperones. Notably, previous work in yeast, worms, and mouse neurons all showed that STI1 protects organisms against stressors and amyloid-like …

Having A High-Activity Catechol-O-Methyltransferase Allele Is Associated With Elevated Anxiety And Lower Salivary Dehydroepiandrosterone But Also Lower Alpha Amylase In Children With Chromosome 22q11.2 Deletion Syndrome., Jessie Beebe

University of New Orleans Theses and Dissertations

Chromosome 22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous deletion located on the long arm of chromosome 22. The most common deletion sizes affect between 30 and 90 genes. Individuals with 22q11.2DS may develop serious developmental and psychiatric disorders. The phenotype is highly variable, however, and may be influenced by allelic variation of the retained copies of genes covered by the deletion. I set out to examine the effects of two genes, catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH), in relation to anxiety in children and adolescents with 22q11.2DS. Individuals with the major COMT allele (higher activity) have significantly higher anxiety …

An End-To-End Cnn With Attentional Mechanism Applied To Raw Eeg In A Bci Classification Task, Elnaz Lashgari, Jordan Ott, Akima Connelly, Pierre Baldi, Uri Maoz

Psychology Faculty Articles and Research

Objective. Motor-imagery (MI) classification base on electroencephalography (EEG) has been long studied in neuroscience and more recently widely used in healthcare applications such as mobile assistive robots and neurorehabilitation. In particular, EEG-based motor-imagery classification methods that rely on convolutional neural networks (CNNs) have achieved relatively high classification accuracy. However, naively training CNNs to classify raw EEG data from all channels, especially for high-density EEG, is computationally demanding and requires huge training sets. It often also introduces many irrelevant input features, making it difficult for the CNN to extract the informative ones. This problem is compounded by a dearth of training …

Exercise Training Rescues Increased Brain Isf Aβ Caused By Chronic Isolation Stress In App/Ps1 Transgenic Mice, Lydia M. Holtmann

MSU Graduate Theses

Alzheimer’s Disease (AD) is a progressive brain disorder that destroys memory and cognition thought to be initiated through the build-up of the amyloid-beta (A) peptide. The A peptide aggregates, slowly forming into insoluble plaque substances that destroy the brain and worsen patient’s symptoms over time. Studies have shown that chronic isolation stress (CIS) increases the A peptide soluble and insoluble levels in the brain and that exercise training decreases these levels in transgenic mouse models of AD. We sought to determine if an exercise training regimen would rescue the increase in Aβ levels caused by CIS in the APP/PS1 transgenic …

Neuronal Migration In Developmental Hyperserotonmia: Assessment Of Vesicular Glutamate In The Raphe Nuclei, Trey M. Shupp

MSU Graduate Theses

The neurotransmitter serotonin is involved in the early development of the central nervous system and the organization of neurons throughout the cerebral cortex and cerebellum. It is proposed that serotonin indirectly interacts with cells in the marginal zone of the cerebral cortex known as Cajal-Retizus (CR) cells. These cells secrete the extracellular matrix protein reelin, which is known for its role in neuronal organization and migration during early neural development. It has been observed that low levels of serotonin are associated with similarly low levels of reelin during development and have been reported to result in disorganization of neurons in …

Elucidating The Modulatory Role Of Dopamine In The C. Elegans Chemosensory Ash Neuron, Cory Kunkel

Electronic Theses, Projects, and Dissertations

The neurotransmitter dopamine regulates chemosensory avoidance behavior in the model organism Caenorhabditis elegans. Avoidance behaviors are mediated by the polymodal ASH nociceptive sensory neurons, and behavioral avoidance of stimuli detected by ASH is less robust when dopamine signaling is impaired. We are investigating the neural response of the ASH neurons to various stimuli; our investigation includes the behavioral and physiological responses from the ASH neurons as dopamine signaling is manipulated to better understand the effects of dopamine on these sensory neurons. We hypothesize that dopamine plays a regulatory role on the ASH neurons, lessening the response of the ASH …

The Balance Of Excitation And Inhibition And Its Influence On Cortical States And Rett Syndrome, Jingwen Li

Graduate Theses and Dissertations

Our brain consists of billions of neurons, properly coordinating to process information and realize brain functions. Among them, there are two types of neurons: excitatory neurons and inhibitory neurons. The firing of excitatory neurons increases the membrane potential of downstream neurons, and thus excites other neurons to fire. The firing of inhibitory neurons, in contrast, decreases the membrane potential of downstream neurons, and thus inhibits other neurons to fire. The interplay of excitatory and inhibitory neurons shape the spiking activity in the population. Thus, the `balance of excitation and inhibition' plays an important role in cortical processing and brain functions. …

Microfabrication And Electrochemical Characterization Of A Novel Su-8 Probe With An Array Of Individually Addressable Electrodes Suitable For Redox Cycling Experiments In Ultra-Small Volumes, Mahsa Lotfi Marchoubeh

Graduate Theses and Dissertations

Redox cycling is an electrochemical technique that utilizes closely spaced generator and collector electrodes to cycle reversible redox species between their oxidative states. With advantages in signal amplification, selectivity of species based on their electrochemical reaction mechanism, and limited or no background subtraction, this technique is well suited for selective detection of important electrochemically active molecules such as dopamine at basal or slowly changing levels.

Miniaturized medical devices have become an area of great interest for measurement of chemicals in limited volumes with low concentrations or in sensitive tissues. A probe on a polymeric SU-8 substrate with suitable dimensions and …

Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the …

The Neurological Asymmetry Of Self-Face Recognition, Aleksandra Janowska, Brianna Balugas, Matthew Pardillo, Victoria Mistretta, Katherine Chavarria, Janet Brenya, Taylor Shelansky, Vanessa Martinez, Kitty Pagano, Nathira Ahmad, Samantha Zorns, Abigail Straus, Sarah Sierra, Julian Keenan

Department of Biology Faculty Scholarship and Creative Works

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990s brought about systematic attempts to isolate the underlying neural basis of self-face recognition. These studies, including some of the first fMRI (functional magnetic resonance imaging) examinations, revealed a right-hemisphere bias for self-face recognition in a diverse set of regions including the insula, the dorsal frontal lobe, the temporal parietal junction, and the medial temporal cortex. In this systematic review, we provide confirmation of these data (which are …

Sites Of Circadian Clock Neuron Plasticity Mediate Sensory Integration And Entrainment, Maria P. Fernand, Hannah L. Pettibone, Joseph T. Bogart, Casey J. Roell, Charles E. Davey, Ausra Pranevicius, Khang V. Huynh, Sara M. Lennox, Boyan Kostadinov, Orie T. Shafer

Publications and Research

Networks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. …

Blocking Pirb Function Increases Dendritic Spine Density In The Prefrontal Cortex Of Adult Rats, Hannah J. Macneil

Electronic Thesis and Dissertation Repository

Schizophrenia is a psychotic disorder consisting of positive, negative, and cognitive symptoms. While patients currently have access to treatments for the positive and negative symptoms, no satisfactory treatment exists to alleviate the cognitive deficits, which cause severe impairments to the quality of life of patients and their families. Although the mechanisms underlying the cognitive deficits of schizophrenia are not clear, a decreased dendritic spine density on layer 3 pyramidal neurons in the dorsolateral prefrontal cortex has been strongly implicated. Generally, the adult brain is not permissive to the formation of new dendritic spines. Recently, an immune receptor called paired immunoglobulin-like …

Severe Covid-19 In Alzheimer’S Disease: Apoe4’S Fault Again?, Nian Xiong, Martin R. Schiller, Jingwen Li, Xiaowu Chen, Zhicheng Lin

Life Sciences Faculty Research

Challenges have been recognized in healthcare of patients with Alzheimer’s disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE …