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Articles 1 - 30 of 1029
Full-Text Articles in Medical Sciences
The Role Of 14-3-3 Proteins In The Pro-Inflammatory Response Of Microglia And The Neuronal Stress Response To Trichloroethylene Exposure, William Stone
ETDs from 2020-2029
ABSTRACT This dissertation examines how 14-3-3 proteins, with a focus on the 14-3-3θ iso-form, regulate signaling pathways relevant to neurodegeneration. While tradition-ally described as molecular hubs that organize protein–protein interactions, our work reveals how 14-3-3 function is shaped by environmental insults, namely bac-terial and neurotoxicant exposures, and how its disruption contributes to disease-associated processes. Two complementary approaches were used, focusing on microglial inflammatory signaling and neuronal responses to an environmental neurotoxicant, to define a broader role for 14-3-3 proteins in disease associated pathways in the brain. Chapter I identifies 14-3-3 proteins as modulators of microglial activation. Disrup-tion of 14-3-3 interactions …
The Role Of Mitochondrial And Lysosomal Damage In Neurotoxicity From Parkinson 'S-Related Environmental Exposures, Neda Ilieva
The Role Of Mitochondrial And Lysosomal Damage In Neurotoxicity From Parkinson 'S-Related Environmental Exposures, Neda Ilieva
ETDs from 2020-2029
Parkinson's disease (PD) is a progressive motor neurodegenerative disorder with a predominantly idiopathic etiology. More recently, however, the contribution of exogenous risk factors such as environmental contaminants has become of interest. Some endogenous genetic risk factors have been well characterized, but the mechanisms by which exogenous insults, such as environmental contaminants, drive dopaminergic neurodegeneration remain incompletely understood. This dissertation will address how environmental contaminants converge on mitochondrial and lysosomal dysfunction to activate parallel neurotoxic signaling pathways, with a focus on the LRRK2 kinase and the cGAS-STING innate immune pathway. Chapter 2 demonstrates that pharmacological inhibition of LRRK2 kinase activity protects …
Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster
Neuroinflammation And Neuropathology In A Novel Tau, Amyloid-Beta And Alpha-Synuclein Co-Pathology Model, Jhodi Mickayla Webster
ETDs from 2020-2029
Neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson disease (PD) often present with overlapping proteinopathies rather than aggregated proteins in isolation. Amyloid-β (Aβ) and phosphorylated tau are found in a substantial proportion of idiopathic PD cases, while α-synuclein (α-syn) pathology is present in over half of AD cases. The presence of these co-pathologies is associated with accelerated cognitive decline and increase mortality in these patients. In parallel, neurodegenerative diseases are increasingly recognized as being shaped by interactions between central nervous system (CNS) pathology and the immune system. Despite this, most experimental animal models of neurodegenerative disease examine single pathologies in …
From Transcriptome To Function: Multimodal Characterization Of Transcriptionally Defined Ventral Tegmental Area Dopamine Neurons, Natalie Dalton Fitzgerald
From Transcriptome To Function: Multimodal Characterization Of Transcriptionally Defined Ventral Tegmental Area Dopamine Neurons, Natalie Dalton Fitzgerald
ETDs from 2020-2029
Substance use disorder is a complex neurobiological disease characterized by impaired control over drug taking and drug seeking. Drugs of abuse exert their reinforcing effects largely through dopaminergic (DAergic) projections from the ventral tegmental area (VTA) to the nucleus accumbens, where all drugs of abuse increase DA transmission. Beyond reward processing and reward learning, the VTA contributes to a range of psychiatric conditions, including schizophrenia and attention-related disorders. Although DA signaling has long been a major focus of addiction research, recent transcriptomic studies have revealed substantial heterogeneity of cell types within the VTA. Previous work from our lab identified two …
Investigating The Effects Of Increased O-Glcnaylation On Pathology In Alzheimer’S Disease, Melissa Louise Garcia
Investigating The Effects Of Increased O-Glcnaylation On Pathology In Alzheimer’S Disease, Melissa Louise Garcia
ETDs from 2020-2029
Alzheimer’s disease (AD) is currently the 7th leading cause of death, with few treatment options. It is known that AD pathology begins 20-30 years before clinical symptoms manifest. Some of the earliest pathological changes occur in glial cells of the hippocampus, causing them to become chronically reactive, as well as the accumulation of Amyloid-β (Aβ) in the hippocampus and hyperphosphorylated Tau (pTau) in the locus coeruleus, resulting in dysfunction of the noradrenergic (NA) system. Preclinical studies have shown promise in the abilities of the post-translational modification O-linked β-N-acetylglucosamine (O-GlcNAc). O-GlcNAc is a tightly regulated reversible enzymatic modification controlled by the …
Characterizing The Role Of The Paraventricular Nucleus Of The Thalamus D2r+ Neurons In Interoceptive Predictions, Briana Machen
Characterizing The Role Of The Paraventricular Nucleus Of The Thalamus D2r+ Neurons In Interoceptive Predictions, Briana Machen
ETDs from 2020-2029
Interoceptive predictions are internal models through which the brain anticipates future bodily states based on past experiences and environmental cues. Under healthy conditions, these predictions allow organisms to anticipate physiological needs and proactively adjust behavior to maintain homeostasis. When these processes become dysregulated, however, environmental cues can trigger maladaptive physiological responses. Although interoceptive prediction is increasingly recognized as a key mechanism underlying adaptive behavior, the neuronal circuits responsible for generating these predictions remain poorly understood. The paraventricular nucleus of the thalamus (PVT) receives convergent inputs from brain regions involved in processing both interoceptive signals and exteroceptive cues, positioning it to …
Integrated Proteomics To Understand The Role Of Neuritin-1 (Nrn1) As A Molecular Mediator Of Synaptic Resilience In Alzheimer’S Disease, Derian Pugh
ETDs from 2020-2029
Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently affects approximately 6.9 million people in the United States. By 2060, the number of people age 65 and older with AD is projected to reach 13.8 million, barring the development of disease-altering therapies to prevent, slow or cure AD. Thus, there is a need for progress in the understanding of AD pathophysiology, as well as in the development of diagnostic and therapeutic interventions. Approximately one-third of individuals without dementia at the time of death are found to harbor high levels of amyloid-beta …
Identifying The Neurobiological Substrates Of Gulf War Illness, Chloe Lisette Jones
Identifying The Neurobiological Substrates Of Gulf War Illness, Chloe Lisette Jones
All ETDs from UAB
Gulf War Illness (GWI) affects approximately 30% of veterans who served in the 1991 Persian Gulf War and is characterized by chronic pain and fatigue, as well as cognitive, mood, gastrointestinal, and respiratory symptoms. Animal research has suggested that GWI is caused by a combination of neurotoxicants such as nerve gas, anti-nerve agent pills, and pesticides, though a definitive pathophysiological model has not been established. In this human observational study, 20 veterans with GWI and 20 healthy Gulf War veterans (HV) underwent whole-brain magnetic resonance spectroscopy (MRS) to non-invasively measure several metabolites associated with neuroinflammation. Whole blood was also collected …
A High-Salt Diet Modulates Renal Afferent Nerve Activity; Potential Role Of The Endothelin System, Jiaxi Shen
A High-Salt Diet Modulates Renal Afferent Nerve Activity; Potential Role Of The Endothelin System, Jiaxi Shen
All ETDs from UAB
Hypertension is a prevalent disease around the world. Increased blood pressure leads to a higher risk of stroke and coronary heart disease. Diet, lifestyle, and gene regulation are potential causative factors, and salt-sensitive hypertension is one common types of hypertension. In response to a high-salt diet, blood pressure may elevate with increasing risks of cardiovascular disease (CVD). Endothelin-1, which binds to endothelin A (ETA) and B (ETB) receptors, is strongly involved in controlling the blood vessels and sensory nerve signaling pathway between the kidney and the central nervous system during high salt dietary challenge. The function of the ETB receptor …
Myelin Mapping In Psychosis, Victoria Lynn King
Myelin Mapping In Psychosis, Victoria Lynn King
All ETDs from UAB
It is well established that myelin in the central nervous system is an axonal insulator which speeds the conduction velocity of action potentials. However, its role in the cortex has also been shown to support metabolic demands and aid in cortical plasticity. Myelin develops throughout childhood and adolescence from sensorimotor areas to association areas and peaks during adolescence. Importantly, this is the same time that psychosis-spectrum disorders (PSDs) begin to present clinically; thus, given the critical role of myelination in shaping the mature cortex, disruptions in this process – particularly during adolescence – are thought to partially explain the onset …
Impact Of Alpha-Synuclein Aggregation On Corticostriatal Synaptic Function And Morphology, Charlotte Franziska Brzozowski
Impact Of Alpha-Synuclein Aggregation On Corticostriatal Synaptic Function And Morphology, Charlotte Franziska Brzozowski
All ETDs from UAB
Lewy Body Dementias (LBDs), including Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB), are defined by α-synuclein (α-syn) accumulation in Lewy Pathology (LP). LP is abundant in cortical layer V intratelencephalic (IT) neurons, a subset of neurons that also degenerate in the pre-supplementary motor area (preSMA) in humans, which is homologous to the secondary motor cortex (M2) in mice, as observed in PD postmortem tissue. IT neuron projections to the striatum are an intrinsic part of the motor basal ganglia circuitry, believed to modulate cognitive aspects of executive motor control, such as updating motor plans. M2 projections to …
Amygdala Npy+ Interneurons Are Activated By Aversive Stim-Uli, Patric Perez
Amygdala Npy+ Interneurons Are Activated By Aversive Stim-Uli, Patric Perez
All ETDs from UAB
Neuropeptide Y (NPY) serves as a critical endogenous anxiolytic and stress-buffering molecule, yet the temporal and spatial dynamics of NPY+ cells during fear learning re-main unknown. Temporal dynamics can be measured with in vivo calcium imaging tech-niques, which enable real-time monitoring of cell-type-specific neural activity in freely behaving animals. Snapshots of neuronal activation can be measured using c-Fos im-munohistochemistry, thereby providing excellent spatial resolution. Here, I employ cut-ting-edge approaches to characterize the temporal and spatial activation patterns of NPY+ cells in amygdala, a key fear-regulating brain region negatively impacted by aversive events. I first used in vivo fiber photometry, together …
Understanding Psychotic Disorders Using Normative Modeling-Derived Individual-Level Brain Structural Abnormalities, Natalie Remiszewski
Understanding Psychotic Disorders Using Normative Modeling-Derived Individual-Level Brain Structural Abnormalities, Natalie Remiszewski
All ETDs from UAB
Psychosis is an heterogenous condition that occurs in many psychiatric disorders. It has a variable symptom presentation and recent initiatives have suggested that investigating the underlying neurobiology of psychiatric disorders rather than their symptomatology would provide a more accurate picture for diagnosis, prognosis, and treatment. Grey matter has been implicated in the pathophysiology of psychosis and psychotic disorders, though significant natural variation due to age and sex have impeded the distinction of pathologically relevant grey matter abnormalities in psychosis. Additionally, case-control approaches to exploring grey matter abnormalities in psychotic disorders often obscure subtle variation in individuals. Here, we utilize a …
Identifying Functional Regional Changes In Patients With Parkinson’S Disease And Freezing Of Gait, Taylor Robin Davis
Identifying Functional Regional Changes In Patients With Parkinson’S Disease And Freezing Of Gait, Taylor Robin Davis
All ETDs from UAB
Freezing of gait (FOG) affects anywhere from 20-80% of those with Parkinson’s Disease (PD) with the prevalence increasing with disease severity and length. This detrimental symptom is unpredictable and poorly characterized, which adds to the negative experience of FOG as it is difficult to treat. Using resting-state fMRI (rs-fMRI), we set out to determine the functional changes in those with PD-FOG and map onto regions of the brain where signal power, measured using fractional amplitude of low-frequency fluctuations (fALFF), synchronicity, as measured by regional homogeneity (ReHo), and strength and direction of intra-network connections as measured by static effective connectivity, are …
Understanding Visual Memory Encoding And The Effects Of Endurance Exercise In Healthy Adults And People With Temporal Lobe Epilepsy, Brandon Steve Mitchell
Understanding Visual Memory Encoding And The Effects Of Endurance Exercise In Healthy Adults And People With Temporal Lobe Epilepsy, Brandon Steve Mitchell
All ETDs from UAB
The visual memory encoding (VME) of indoor and outdoor scenes is a complex cognitive process that primarily utilizes the bilateral hippocampi and medial temporal lobe (MTL) structures along the parahippocampal gyrus. Alpha and theta frequency band oscillations are important in the processing of visual information and memory formation, respectively. We completed hree studies investigating the cognitive process of VME in healthy adults and people with temporal lobe epilepsy (pwTLE). The first study was cross-sectional and utilized a functional magnetic resonance imaging (fMRI)-constrained magnetoencephalography (MEG) analysis in healthy adults to explore VME. The fMRI results were used as spatial priors to …
Murder On The Axonal Express: Synucleinopathy Disruption Of 14-3-3 Protein-Protein Interactions Impairs Axonal Trafficking, Frank Sanders Pair
Murder On The Axonal Express: Synucleinopathy Disruption Of 14-3-3 Protein-Protein Interactions Impairs Axonal Trafficking, Frank Sanders Pair
All ETDs from UAB
14-3-3s are a family of proteins highly expressed in the brain. These proteins exert their functions mainly through protein-protein interactions (PPIs) and have thousands of binding partners. 14-3-3s have been shown to be present in pro-teinaceous aggregates of alpha-synuclein (αsyn), a pathological hallmark of synucleinopathies. This includes such diseases as Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). 14-3-3 proteins, particularly the 14-3-3θ isoform, have been shown to be protective in multiple synucleinopathy models. However, reduced soluble levels of 14-3-3s and increased phosphorylation of 14-3-3θ at S232 observed in synucleinopathies like DLB may impair their protec-tive ability, potentially due …
Understanding The Functional Consequence Of Cul3 Deletion In The Mammalian Brain, Prathibha Sekar
Understanding The Functional Consequence Of Cul3 Deletion In The Mammalian Brain, Prathibha Sekar
All ETDs from UAB
Polyubiquitination is a post-translational modification which often results in degradation of the ubiquitin-tagged protein. E3 ubiquitin ligases are multi-subunit protein complexes that assist in this ubiquitination process. Multiple genes that play a role in ubiquitination are implicated in autism spectrum disorder, a highly heterogeneous neurodevelopmental disorder. CULLIN3 (CUL3), a scaffolding protein part of the E3 ubiquitin ligase complex, is the product of a high-risk autism gene implicated across multiple large scale sequencing studies of autism patients. Additionally, CUL3 haploinsufficiency is associated with a syndromic disorder called NEDAUS (Neurodevelopmental disorder with or without autism or seizures) characterized by intellectual disability (ID), …
An Analysis Of Gamma-Aminobutyric Acid Levels With Structural And Functional Connectivity In Antipsychotic Medication-Naïve First Episode Psychosis Patients, Genelle Dano Samson
An Analysis Of Gamma-Aminobutyric Acid Levels With Structural And Functional Connectivity In Antipsychotic Medication-Naïve First Episode Psychosis Patients, Genelle Dano Samson
All ETDs from UAB
Schizophrenia is a complex psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and abnormalities in emotional expression, social interaction, and motivation. Cognitive deficits and alterations in perception are core features of psychosis spectrum disorders, though the neurobiological bases of these impairments are not thoroughly understood. Examination of the structures responsible for cognition, along with how their connectivity and neurochemistry are altered in psychosis, is crucial to understanding and treating schizophrenia. Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system and plays a crucial role in the regulation of neuronal activity. Evidence from animal models and postmortem …
Insights Into Rett Syndrome: Social Behavior, Bdnf-Trkb Signaling, And Dendritic Spines, Destynie Medeiros
Insights Into Rett Syndrome: Social Behavior, Bdnf-Trkb Signaling, And Dendritic Spines, Destynie Medeiros
All ETDs from UAB
Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females, caused by pathogenic variants in the X-linked MECP2 gene, which encodes the transcriptional modulator Methyl-CpG binding protein 2 (MeCP2). RTT is characterized by motor deficits, loss of speech, autistic features, and intellectual disability. A key gene regulated by MeCP2 is BDNF, encoding the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improves several RTT phenotypes in mouse models. Due to BDNF's low blood-brain barrier permeability, we tested LM22A-4, a brain-penetrant small molecule ligand of TrkB receptors, on …
Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan
Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan
All ETDs from UAB
Cognitive control enables flexible, goal-directed behavior by dynamically adjusting our actions in response to changing task demands. This dissertation investigates the neural mechanisms underlying proactive and reactive cognitive control, particularly focusing on the dorsolateral prefrontal cortex (dlPFC) and the dorsal anterior cingulate cortex (dACC) during tasks that require response inhibition and conflict processing. Using intracranial electroencephalography (iEEG) recordings from human participants, this research examines the distinct roles of oscillatory activity in these regions in both short-term reactive adjustments and long-term proactive control strategies. Chapter 2 explores the role of low-frequency oscillations in the mid-rostral dlPFC during motor inhibition, revealing that …
The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop
The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop
All ETDs from UAB
Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …
Social Dominance And Cortical Neuronal Synchrony In Male Mecp2 Knockout Mice, Cesar Andres Acevedo Triana
Social Dominance And Cortical Neuronal Synchrony In Male Mecp2 Knockout Mice, Cesar Andres Acevedo Triana
All ETDs from UAB
Social behaviors are critical for the survival of individuals, and their dysfunction is common in several neuropsychiatric and neurodevelopmental disorders including autism, where impaired sociability is one of the core diagnostic symptoms and compromises the interpretation of social cues, with an apparent lack of interest in others. Among the neurodevel opmental disorders associated with autism, Rett syndrome (RTT) is a disorder predominantly affecting females and caused by spontaneous loss-of-function mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator MeCP2 that regulates many critical genes. RTT individuals have impaired motor, cognitive, and social abilities most of which are recapitulated …
Reelin Regulation Of Striatal Physiology And Cocaine Reward, Kasey Lynn Brida
Reelin Regulation Of Striatal Physiology And Cocaine Reward, Kasey Lynn Brida
All ETDs from UAB
Drugs of abuse activate defined neuronal populations in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc neuron participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neurons within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early …
Investigating Potential Therapeutic Vulnerabilities And Elucidating Molecular Mechanisms For The Tumor Suppressors Nfkbia And Anxa7 In Diffuse Gliomas, Aran Merati
All ETDs from UAB
Gliomas, and especially diffuse gliomas, can be a devastating disease when attempting treatment in the clinic. Diffuse gliomas are typically malignant and pose definitive problems with respect to patient care predominantly due to their ability to exist outside of the bulk tumor by invading into the surrounding brain parenchyma. Consequently, not every cancerous cell can be fully removed by surgical resection and therapeutic resistance, so the stem-like population left behind can repopulate a recurrent tumor from a single cell. There is a desperate need for pinpointing novel therapeutic vulnerabilities in diffuse gliomas, which could potentially involve the targeting of key …
Maternal Immune Activation Causes Oligodendrocyte Deficits In The Hypothalamus, Kate Miller
Maternal Immune Activation Causes Oligodendrocyte Deficits In The Hypothalamus, Kate Miller
All ETDs from UAB
Maternal immune activation (MIA) refers to the occurrence of an inflammatory immune response during any stage of pregnancy. This manifests as the upregulation of proinflammatory cytokines and can be caused by air pollution, obesity, or viral infection. When this occurs during the first trimester in humans, it increases the offspring’s susceptibility to developing neuropsychiatric disorders such as autism (ASD) and schizophrenia (SZ), in males more commonly than females. In addition to behavioral manifestations of neuropsychiatric disorders, metabolic syndrome (MetS) is a common comorbidity, defined as the co-occurrence of three or more symptoms including but not limited to hyperlipidemia, hypertension, and …
Parsing Clinical And Neurobiological Heterogeneity In First-Episode Psychosis Patients With And Without Features Of The Deficit Syndrome Of Schizophrenia, Matheus Teles Gomes De Araujo
Parsing Clinical And Neurobiological Heterogeneity In First-Episode Psychosis Patients With And Without Features Of The Deficit Syndrome Of Schizophrenia, Matheus Teles Gomes De Araujo
All ETDs from UAB
Schizophrenia is highly heterogeneous in its neurobiological and clinical presentations, which hinders attempts to understand its pathophysiology, limits efforts to identify biomarkers, and deters optimal patient care. A way to parse clinical heterogeneity is to subtype patients based on clinical presentations. The deficit syndrome (DS) is a possible subtype, characterized by primary and enduring negative symptoms. Evidence for neurobiological abnormalities dissociating DS from other forms of schizophrenia is inconsistent as most studies do not account for heterogeneity within patient groups due to limitations of group-level comparisons. The question remains whether DS presents a unique and less heterogeneous neurobiological phenotype. The …
Investigating Molecular Mechanisms Behind Neuronotypic Gba1 Mutations In Lewy Body Dementias, Casey Mahoney-Crane
Investigating Molecular Mechanisms Behind Neuronotypic Gba1 Mutations In Lewy Body Dementias, Casey Mahoney-Crane
All ETDs from UAB
Nonmotor deficits are present in nearly all Parkinson’s disease (PD) patients, with ~80% of these patients developing dementia. Importantly, expression of the severe GBA1 L444P heterozygous mutation increases the risk for Parkinson’s disease devel-opment by 5.43 times compared to mild mutation carriers. Currently, many PD treat-ments predominately focus motor symptoms, while treatments for nonmotor symptoms, such as visual-spatial difficulties and dementia, focus on symptom management and continue to remain elusive. Therefore, understanding the molecular mechanisms behind these nonmotor symptoms is essential for the development of effective therapeutics leading to slower disease progression. The work presented in this dissertation sought to …
O-Glcnacylation And Modulation Of Gabaergic Transmission, Shekinah Phillips
O-Glcnacylation And Modulation Of Gabaergic Transmission, Shekinah Phillips
All ETDs from UAB
Changes in the strength of GABAergic transmission is heavily influenced by posttranslational modifications and allosteric modulators like benzodiazepines and neurosteroids. O-GlcNAcylation (O-GlcNAc) is a post-translational modification that is tightly regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which add or remove the O-GlcNAc moiety of β–N-acetylglucosamine to serine and threonine residues on proteins, respectively. Published reports from our lab have demonstrated that an acute increase in O-GlcNAcylation induces a long-term depression (LTD) of evoked GABAAR mediated IPSCs (eIPSCs) and reduces the amplitude and frequency of spontaneous IPSC (sIPSC) in hippocampal principal cells, however the mechanism in which this occurs is …
Elementary Cone Photoreceptor Signals In V1 Neurons, Cyril Nyankerh
Elementary Cone Photoreceptor Signals In V1 Neurons, Cyril Nyankerh
All ETDs from UAB
Daylight vision is initiated by the activation of cone photoreceptors in the retina in response to light, thereby generating spatial and temporal patterns of photoreceptor signals. Subsequent to this, the signals are combined and processed in downstream neural circuits, ultimately contributing to the formation of receptive fields of neurons in primary visual cortex (V1). Recent advances in adaptive optics (AO) have enabled imaging of the retina with near diffraction limited resolution, allowing for the probing of the visual system's processing at the resolution of individual cones. The central theme of this dissertation characterizes quantitively and qualitatively the physiological responses of …
The T Cell Response In A Mouse Model Of Multiple System Atrophy, Nicole Jane Corbin-Stein
The T Cell Response In A Mouse Model Of Multiple System Atrophy, Nicole Jane Corbin-Stein
All ETDs from UAB
Multiple System Atrophy (MSA) is a fatal and rare demyelinating synucleinopathy, characterized by the accumulation of alpha-synuclein (α-syn) in glial cytoplasmic inclusions (GCIs) within oligodendrocytes. This condition is marked by neuroinflammation, demyelination, and neurodegeneration in areas showing GCI pathology, involving antigen presentation by myeloid cells and infiltration of CD4+ and CD8+ T cells. Despite strong evidence of neuroinflammation in post-mortem MSA tissue, the specific mechanisms driving the disease pathogenesis remain elusive. In prior research using the Olig001-SYN mouse model, which involves the modified AAV vector, it was shown that depleting CD4+ T cells can reduce neuroinflammation and demyelination. Notably, this …