Neurosciences Commons^™

The Effect Of Progranulin On Lysosomal Function In Bv2 Cells, Michelle Park

All ETDs from UAB

Neurodegenerative diseases afflict nearly 7 million people in United states, constituting a significant portion of the 600 known neurological disorders. Characterized by the gradual loss of neurons and axons within the central nervous system (CNS), these conditions stem from chronic inflammatory activation of the brain. Chronic inflammation disrupts important processes such as autophagy lysosome pathway, a self-degradative process that eliminates protein aggregates and damaged organelles. Trehalose, a non-reducing disaccharide that triggers autophagic flux in neuronal cells and promotes the clearance of protein aggregates; however, without understanding the mechanism behind how trehalose affects these functions, it lacks value. In our study, …

The Aphasia Recovery Cohort, An Open-Source Chronic Stroke Repository, Makayla Gibson, Roger Newman-Norlund, Leonardo Bonilha, Julius Fridriksson, Gregory Hickok, Argye E. Hillis, Dirk B. Den Ouden, Chris Rorden

Communication Sciences and Disorders Faculty Articles and Research

Sharing neuroimaging datasets enables reproducibility, education, tool development, and new discoveries. Neuroimaging from many studies are publicly available, providing a glimpse into progressive disorders and human development. In contrast, few stroke studies are shared, and these datasets lack longitudinal sampling of functional imaging, diffusion imaging, as well as the behavioral and demographic data that encourage novel applications. This is surprising, as stroke is a leading cause of disability, and acquiring brain imaging is considered standard of care. The first release of the Aphasia Recovery Cohort includes imaging data, demographics and behavioral measures from 230 chronic stroke survivors who experienced aphasia. …

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

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

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

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 …

Beyond Chronic Fatigue: Studying The Role Of Neuroinflammation, Glutamate, And Glutamine, Indonesia Alohn Jordan

All ETDs from UAB

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multifaceted disease characterized by persistent, severe fatigue lasting six months or longer that is not relieved by rest. An estimated 20 million people worldwide suffer from ME/CFS. ME/CFS has long been suspected to be a post-viral illness, as viral infections can stimulate inflammatory cytokine production. Millions of coronavirus disease 2019 (COVID-19) patients are also predicted to develop persistent symptoms that mimic ME/CFS symptomology after the resolution of the acute infection, referred to as Post-Acute Sequelae of COVID-19 (PASC). Inflammatory mediators produced by sustained microglia activation have been shown to lead to illness …

Impact Of Alpha-Synuclein Aggregates On Synaptic Structure In The Amygdala, Nolwazi Zakithi Gcwensa

All ETDs from UAB

Parkinson’s disease is the most common motor neurodegenerative and is characterized by intracellular inclusions of misfolded protein α-synuclein termed Lewy Pathology. At least 80% of PD sufferers also experience non-motor symptoms along with, and sometimes preceding, the motor symptoms. Symptoms such as apathy, hallucinations, anxiety and depression could be caused by α-synuclein inclusions causing dysfunction in the amygdala. Lewy pathology in the amygdala of PD patients is robust and has also been observed in a number of other diseases like Dementia with Lewy Bodies and Alzheimer's disease. In our lab, we have shown that using preformed fibrils to induce α-synuclein …

Exploring The Use Of Bimodal Transcranial Direct Current Stimulation To Enhance Movement In Individuals With Patellofemoral Pain—A Sham-Controlled Double Blinded Pilot Study, Kai-Yu Ho, Connan Wallace, Jeno Aquino, Bryce Broadwell, Makenzie Whimple, Jing Nong Liang

Physical Therapy Faculty Research

Introduction: In individuals with patellofemoral pain (PFP), addressing increased knee valgus during weight-bearing activities typically involves strengthening weak hip muscles. However, recent literature highlights the role of altered descending central control in abnormal movements associated with PFP. While transcranial direct current stimulation (tDCS) has demonstrated the capacity to enhance neuroplasticity, its application targeting the corticomotor function of gluteal muscles in PFP remains unexplored. This study aimed to investigate the effects of combining bimodal tDCS with exercise on frontal plane kinematics in individuals with PFP. The hypothesis was that bimodal tDCS, specifically targeting the corticomotor function of the gluteal muscles, would …

Multimodal Mixing Convolutional Neural Network And Transformer For Alzheimer’S Disease Recognition, Junde Chen, Yun Wang, Adnan Zeb, M. D. Suzauddola, Yuxin Wen

Engineering Faculty Articles and Research

Early recognition of Alzheimer’s disease (AD) and its precursor state, mild cognitive impairment (MCI), is pivotal in interrupting the progression of the disease and providing suitable treatment. Recent development in deep learning techniques has drawn great research attention for improving the efficacy of AD recognition. However, numerous current methods solely utilize data from a single auxiliary domain, limiting their ability to harness valuable intrinsic insights from multiple domains. To cope with the challenge, this paper is devoted to establishing an innovative multimodal medical data fusion model, termed as MMDF, to perform Alzheimer’s disease recognition. Multimodal data including clinical records and …

Navigating Life: Neuroscience And Inclusive Design In Wayfinding Systems, Stephanie Jost, Piper Hutson, James Hutson

Faculty Scholarship

Wayfinding, as conceptualized by Lynch, has transformed from traditional navigation methods reliant on visual cues and landmarks to modern systems that integrate digital technologies and neuroscience. This study addresses the need for accessible and consistent wayfinding systems that accommodate diverse user abilities, particularly in complex environments such as public transit, hospitals, and large institutions. Current systems often lack coordination, clear signage, and comprehensive coverage, leading to navigation challenges. Through a multi-method approach, including literature review and case study analysis, this research evaluates best practices for inclusive wayfinding. Key findings emphasize the importance of consistent visual design, strategic sign placement, and …

Dominant Missense Variants In Srebf2 Are Associated With Complex Dermatological, Neurological, And Skeletal Abnormalities, Matthew J Moulton, Kristhen Atala, Yiming Zheng, Debdeep Dutta, Dorothy K Grange, Wen-Wen Lin, Daniel J Wegner, Jennifer A Wambach, Angela L Duker, Michael B Bober, Lisa Kratz, Carol A Wise, Ila Oxendine, Anas Khanshour, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, F Sessions Cole, Jonathan Rios, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods: We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences …

The Cerebellum Modulates Thirst, Ila Mishra, Bing Feng, Bijoya Basu, Amanda M Brown, Linda H Kim, Tao Lin, Mir Abbas Raza, Amelia Moore, Abigayle Hahn, Samantha Bailey, Alaina Sharp, Juan C Bournat, Claire Poulton, Brian Kim, Amos Langsner, Aaron Sathyanesan, Roy V Sillitoe, Yanlin He, Atul R Chopra

Duncan NRI Faculty and Staff Publications

The cerebellum, a phylogenetically ancient brain region, has long been considered strictly a motor control structure. Recent studies have implicated the cerebellum in cognition, sensation, emotion and autonomic function, making it an important target for further investigation. Here, we show that cerebellar Purkinje neurons in mice are activated by the hormone asprosin, leading to enhanced thirst, and that optogenetic or chemogenetic activation of Purkinje neurons induces rapid manifestation of water drinking. Purkinje neuron-specific asprosin receptor (Ptprd) deletion results in reduced water intake without affecting food intake and abolishes asprosin's dipsogenic effect. Purkinje neuron-mediated motor learning and coordination were unaffected by …

Mondoa And Aki And Aki-To-Ckd Transition, Shihomi Maeda, Shinsuke Sakai, Yoshitsugu Takabatake, Takeshi Yamamoto, Satoshi Minami, Jun Nakamura, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Sho Matsui, Atsuhiro Imai, Ryuya Edahiro, Hitomi Yamamoto-Imoto, Isao Matsui, Seiji Takashima, Ryoichi Imamura, Norio Nonomura, Motoko Yanagita, Yukinori Okada, Andrea Ballabio, Shuhei Nakamura, Tamotsu Yoshimori, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Key Points:

1. The expression of MondoA was decreased in the renal tubules of patients with CKD.

2. Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.

3. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.

Background: Elderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain …

Imaging Markers Of Future Neurodegeneration Following Moderate-Severe Traumatic Brain Injury, Daniel Brennan

Dissertations, Theses, and Capstone Projects

The overall goal of this dissertation was to identify patterns of cerebral atrophy following traumatic brain injury and relate relevant imaging measures to that atrophy. In Chapter 2, we outline a spatiotemporal profile of atrophy in the first year following moderate-severe TBI: prior to 3-months post injury, the frontal and temporal cortices were observed to be thinner than controls, and thalamic volumes were reduced. From 3-12 months post-injury, significant atrophy was observed in white matter, subcortical gray matter structures (including thalamus), and cortical thinning was observed in the parietal and occipital cortices.

In Chapter 3, we identified widespread white matter …

Arcuate Dopaminergic/Gabaergic Neurons Project Within The Hypothalamus And To The Median Eminence, Somya Mittal, Benjamin R Arenkiel, Ariel M Lyons-Warren

Duncan NRI Faculty and Staff Publications

Cotransmission, meaning the release of multiple neurotransmitters from one synapse, allows for increased diversity of signaling in the brain. Dopamine (DA) and γ-aminobutyric acid (GABA) are known to coexpress in many regions such as the olfactory bulb and the ventral tegmental area. Tuberoinfundibular dopaminergic neurons (TIDA) in the arcuate nucleus of the hypothalamus (Arc) project to the median eminence (ME) and regulate prolactin release from the pituitary, and prior work suggests dopaminergic Arc neurons also cotransmit GABA. However, the extent of cotransmission, and the projection patterns of these neurons have not been fully revealed. Here, we used a genetic intersectional …

Leveraging The Science Of Early Life Predictability To Inform Policies Promoting Child Health, Laura M. Glynn, Sabrina R. Liu, Candice Taylor Lucas, Elysia Poggi Davis

Psychology Faculty Articles and Research

Addressing the tremendous burden of early-life adversity requires constructive dialogues between scientists and policy makers to improve population health. Whereas dialogues focused on several aspects of early-life adversity have been initiated, discussion of an underrecognized form of adversity that has been observed across multiple contexts and cultures is only now emerging. Here we provide evidence for “why unpredictability?”, including: 1. Evidence that exposures to unpredictability affect child neurodevelopment, with influences that persist into adulthood. 2. The existence of a translational non-human animal model of exposure to early life unpredictability that can be capitalized upon to causally probe neurobiological mechanisms. 3. …

Heparan Sulfate Roles In Amyloid-Beta Clearance And Alzheimer’S Disease Pathogenesis, Ilayda Ozsan

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease (AD) is the most common form of dementia yet remains without an effective treatment due to its poorly understood etiology. Mounting evidence points to the accumulation and aggregation of amyloid-β peptides (Aβ), which constitute amyloid plaques in the brain, as pivotal in initiating and accelerating AD pathogenesis. Extensive efforts have focused on uncovering the molecular underpinnings and fundamental origins of impaired Aβ metabolism in AD. Heparan sulfate (HS), a linear polysaccharide of the glycosaminoglycan family, co-deposits with Aβ in plaques within the AD brain. It directly binds to and accelerates Aβ aggregation, interacts with key players in Aβ …

Inequality, Prenatal Stress, And Infant Negative Emotionality: Pregnancy As A Marker Of Intergenerational Transmission, Özlü Aran

Electronic Theses and Dissertations

The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that pregnancy is a developmentally sensitive period during which environmental factors can have long term consequences for the pregnant individual and the fetus. This model regards pregnancy as a mechanism for the intergenerational transmission of health. The aim of the current dissertation is to identify sociocultural stressors that put pregnant individuals at risk and understand how stress-responsive hormones might impact infant emotional development after birth. The first study focuses on types of discrimination as sociocultural stressors and how they relate to markers of psychological and physiological stress among pregnant individuals. …

Slow Ramping Emerges From Spontaneous Fluctuations In Spiking Neural Networks, Jake Gavenas, Ueli Rutishauer, Aaron Schurger, Uri Maoz

Psychology Faculty Articles and Research

The capacity to initiate actions endogenously is critical for goal-directed behavior. Spontaneous voluntary actions are typically preceded by slow-ramping activity in medial frontal cortex that begins around two seconds before movement, which may reflect spontaneous fluctuations that influence action timing. However, the mechanisms by which these slow ramping signals emerge from single-neuron and network dynamics remain poorly understood. Here, we developed a spiking neural-network model that produces spontaneous slow ramping activity in single neurons and population activity with onsets ~2 s before threshold crossings. A key prediction of our model is that neurons that ramp together have correlated firing patterns …