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- Aging, Alzheimer Disease, Cerebrovascular Disease, MRI, Neuroimaging (1)
- Animal model, behavior, emotion, pain, preclinical meta-analysis (1)
- Autism, brain development, cerebral organoids, CRLF3, human induced pluripotent stem cells, neurofibromatosis type 1 (1)
- Cognitive deficits, DEND, Hippocampus, KATP, LTP (1)
- FMRI, intrinsic, oscillations, physiology, spontaneous, waves (1)
Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Slo2.1 Channels: A New Molecular Mechanism To Regulate Uterine Excitability, Juan Jose Ferreira
Arts & Sciences Electronic Theses and Dissertations
At the end of pregnancy, the uterus transitions from a non-contractile state to a highly contractile state. Two processes primarily drive this transition. First, from the 28th week of pregnancy until labor, the resting membrane potential of uterine (myometrial) smooth muscle cells (MSMCs) gradually becomes more positive (depolarizes) (Parkington et al. 1999). Second, at the end of pregnancy, MSMCs express more oxytocin receptors and become more sensitive to oxytocin (Kimura et al. 1996). However, the detailed mechanisms by which these processes occur have not been determined. My central hypothesis was that the Na+-activated K+ channel SLO2.1 plays a key role …
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Influence Of Focal Activity On Macroscale Brain Dynamics In Health And Disease, Zachary Pollack Rosenthal
Arts & Sciences Electronic Theses and Dissertations
Macroscopic recordings of brain activity (e.g. fMRI, EEG) are a sensitive biomarker of the neural networks supporting neurocognitive function. However, it remains largely unclear what mechanisms mediate changes in macroscale networks after focal brain injuries like stroke, seizure, and TBI. Recently, optical neuroimaging in animal models has emerged as a powerful tool to begin addressing these questions. Using widefield imaging of cortical calcium dynamics in mice, this dissertation investigates the mechanisms by which focal disruptions in activity alter brain-wide functional dynamics. In two chapters, I demonstrate 1) that focal sensory stimulation elicits state-dependent, global slow waves propagating from primary somatosensory …
Identification Of Multi-Tissue Protein Quantitative Trait Loci And Causal Inference Of Protein Effects In Neurological And Other Complex Human Diseases Via Mendelian Randomization, Chengran Yang
Arts & Sciences Electronic Theses and Dissertations
Alzheimer disease (AD) is the most common neurodegenerative disease, affecting 6.2 million people mostly aged 65 years or older in the United States as of early 2021. AD has been widely studied and characterized worldwide, but there is still no effective treatment or cure. Even the latest FDA-approved treatment, Aducanumab, cannot stop decline or improve cognition. To develop a truly effective treatments, researchers keep discovering genetic and molecular mechanisms underlying the disease. Protein biomarkers are keys to bridge the mechanisms to disease. Here, I first used a high-throughput proteomic dataset from three tissues (CSF, plasma, and brain) with array-based genotype …
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Influence Of Aging And Cerebrovascular Disease On Neuroimaging Measures Of Alzheimer Disease, Lauren Nicole Koenig
Arts & Sciences Electronic Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how Alzheimer disease relates to normal aging and cerebrovascular disease to impact neuroimaging measures in a clinically meaningful way. Both aging and cerebrovascular disease are known to influence measures of Alzheimer disease, making it difficult to separate what changes are attributable specifically to Alzheimer disease. We hypothesize that a better understanding of these relationships will allow future studies to appropriately take these factors into account. In Chapters 2 and 3 we attempt to separate out the influences of normal aging and Alzheimer disease on measures of atrophy. …
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Genetic Risk Factors For Neurodevelopmental Disorders: Insights From Hipsc-Cerebral Organoids, Michelle L. Wegscheid
Arts & Sciences Electronic Theses and Dissertations
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder (NDD) characterized by remarkable phenotypic variability, where affected children manifest a spectrum of central nervous system (CNS) abnormalities, including brain tumors, impairments in attention, behavior, learning disabilities, and an increased incidence of autism spectrum disorder (ASD). A significant barrier to the implementation of precision medicine strategies for children with NF1 is a lack of prognostic risk factors to guide clinical management. However, emerging population-based genotype-phenotype association studies have suggested that the germline NF1 gene mutation may represent one clinically actionable risk factor for NF1-associated neurodevelopmental abnormalities. As a critical step in …
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Causal Function And Bias Correlation Of The Orbitofrontal Cortex In Economic Choices, Shi Weikang
Arts & Sciences Electronic Theses and Dissertations
Economic choices entail two mental processes, value calculation and value comparison (Niehans, 1990). Studies in the last twenty years have shown that neurons in the orbitofrontal cortex (OFC) could support both processes. Namely, in the studies in which monkeys chose between two juice options with various amounts, three functional cell groups had been found in the OFC: offer value cells encode the value of individual juices, chosen juice cells encode the choice in a binary way and chosen value cells encode the value of the chosen juice (Padoa-Schioppa and Assad, 2006). These results suggest a decision circuit within OFC with …
On Arousal And The Internal Regulation Of Brain Function: Theory And Evidence Across Modalities And Species, Ryan Raut
Arts & Sciences Electronic Theses and Dissertations
The brain is an organ. It is subject to the same physiological regulatory processes that engage the rest of the body’s organs, sculpted over hundreds of millions of years to sustain life so effectively. The central message of this thesis is that the holistic functioning of the brain, rather than operating at some level above or independent from these systemic regulatory processes, is deeply related to them. In short, as our limited attention spans might suggest: brain function is internally regulated. I propose that this internal regulation is a primary function of intrinsic brain activity. Chapter 2 provides a theoretical …
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
Arts & Sciences Electronic Theses and Dissertations
ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy
Arts & Sciences Electronic Theses and Dissertations
The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …
Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek
Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek
Arts & Sciences Electronic Theses and Dissertations
Pain and opioid use disorder prevalence, diagnoses of mental health disorders, and rate of suicide have all skyrocketed over the last 30 years as a matrix of public health crises. Each reduces quality of life and installs risk of the others; together, they have burdened our country with nearly unmanageable healthcare challenges. Although the critical demand for novel and more effective therapeutics has been clear for decades, relatively little progress has been made to address pain and its comorbidities. Repeated clinical trial failures have called into question the preclinical evidence upon which they are based. Preclinical models of pain-induced negative …