Neuroscience and Neurobiology Commons^™

Effects Of Optic Nerve Head Astrocyte-Derived Exosomes On Neuronal Survival And Differentiation In Vitro In A Model For Exfoliation Glaucoma, Harsh Nilesh Hariani

Master's Theses

Exfoliation glaucoma (XFG) is characterized by deposition of exfoliation material at the trabecular meshwork thereby blocking aqueous outflow and consequently increasing intraocular pressure (IOP). Elevated IOP initiates glaucomatous biomechanical damage at the optic nerve head (ONH) eventually resulting in retinal neuronal death and vision loss. The major cell type at ONH are ONH astrocytes (ONHA). A chronic downregulation of LOXL1 expression has been reported in ONH of XFG patients. We hypothesized that wild-type and LOXL1 knock-down ONHA derived exosomes have differential effects on neurons in vitro.We here report that ONHAs release exosomes, which can be taken up by astrocytes and …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways, Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric M. Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Neuroscience Faculty Publications

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

The Role Of Melatonin In Biological Rhythms Of Songbirds, Clifford E. Harpole

Theses and Dissertations--Biology

In vertebrates, melatonin is a hormone that is produced and secreted at night and inhibited by light. This unique “darkness-only” expression profile makes it an intellectually appealing candidate for a means of transmitting temporal information to an individual, both time of day and time of year.

In passerine birds, “time of day” information is certainly transmitted via melatonin secretion. The primary producer of systemic melatonin in this family of birds is the pineal gland, and surgical removal of it causes a bird to become arrhythmic in constant conditions. I find that as pinealectomized house sparrows (Passer domesticus) become …

Involvement Of The Sigma-1 Receptor In Methamphetamine-Mediated Changes To Astrocyte Structure And Function, Richik Neogi

Theses and Dissertations--Medical Sciences

Methamphetamine is a highly addictive psychostimulant drug. There are currently no FDA-approved pharmacological treatments for methamphetamine addiction. Pharmacologically, (+)-methamphetamine is a dopamine releasing agent and dopamine transporter substrate that redistributes dopamine from intracellular vesicles via the vesicular monoamine transporter 2 (VMAT2) and reverses the direction of dopamine transport in the dopamine transporter. Methamphetamine, cocaine, and other drugs of abuse are also sigma-1 receptor ligands, and previous studies have demonstrated the role of the sigma-1 receptor in modulating the behavioral and cellular effects of these drugs. However, almost all these studies were conducted in cell culture systems or with emphasis on …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca²⁺ hypothesis of brain aging and dementia. Indeed, many Ca²⁺-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca²⁺ with age was due to increased Ca²⁺ channel density, elevated release from intracellular Ca²⁺ stores, and decreased Ca²⁺ buffering …

Apoe As A Metabolic Regulator In Humans, Mice, And Astrocytes, Brandon C. Farmer

Theses and Dissertations--Physiology

Altered metabolic pathways appear to play central roles in the pathophysiology of late-onset Alzheimer’s disease (AD). Carrier status of the E4 allele of the APOE gene is the strongest genetic risk factor for late-onset AD, and increasing evidence suggests that E4 carriers may be at an increased risk for neurodegeneration based on inherent metabolic impairments. A new appreciation is forming for the role of APOE in cerebral metabolism, and how nutritional factors may impact this role. In chapter 1, the literature on nutritional interventions in E4 carriers aimed at mitigating disease risk is reviewed. Studies investigating the mechanism by which …

Ceramide-Enriched Extracellular Vesicles: A Role In Enhancing Amyloid-Beta Neurotoxicity And Mitochondrial Damage In Alzheimer’S Disease, Ahmed Elsherbini

Theses and Dissertations--Physiology

Alzheimer’s disease (AD) is an age-dependent, progressive, neurodegenerative disorder that is characterized clinically by the impairment of cognitive functions concomitant with behavioral and personality changes. AD is associated with distinct pathological hallmarks, namely, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, extracellular amyloid beta (Aβ) plaques, and marked brain atrophy. Besides their main role as the core component of amyloid plaques, oligomeric Aβ have been shown to be neurotoxic. The exact mechanism of Aβ neurotoxicity is yet to be elucidated.

Recently, a pathogenic function of small extracellular vesicles- also known as exosomes- has been proposed, suggesting that exosomes can transfer …

Intracellular Localization Of The Novel Polyq Protein Fam171b, Dulanjani Rajaguru

All Graduate Theses, Dissertations, and Other Capstone Projects

FAM171B is a relatively uncharacterized protein that contains fourteen consecutive glutamine residues within its primary amino acid sequence; thus it is a polyglutamine (polyQ) protein. PolyQ proteins are interesting because mutations within the polyQ tract have been linked to a number of severe neurodegenerative diseases including Huntingtons Disease (HD). To date, there are minimal published data regarding FAM171B and its molecular function, such that both expression levels and intracellular localization have yet to be definitively determined. Using immunohistochemical and in situ hybridization analyses, our lab has recently found that FAM171B is expressed throughout the mouse brain. This current study attempts …

Neuroanatomy Of The Blackspotted Rockskipper, Entomacrodus Striatus, Pooja Dayal

Williams Honors College, Honors Research Projects

Here I characterized the central neuroanatomy of the Blackspotted Rockskipper, Entomacrodus striatus, native to French Polynesia. The neuroanatomy of E. striatus has not been studied prior to this paper. I used several histology and antibody staining techniques to accomplish this, including Crystal Violet, immunohistochemistry, immunofluorescence, and Bielschowsky’s Silver Nitrate staining. This paper describes the most successful techniques used, identifies major structures in the species’ neuroanatomy, and also explains why studying E. striatus is important in the future of vertebrate research.

Alzheimer's Disease Drug Development Pipeline: 2020, Jeffrey Cummings, Garam Lee, Aaron Ritter, Marwan Sabbagh, Kate Zhong

School of Medicine Faculty Research

© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. Introduction: Alzheimer's disease (AD) is a growing public health concern affecting millions of patients worldwide and costing billions of dollars annually. We review the pipeline of drugs and biologics in clinical trials for the treatment of AD. We use the Common Alzheimer's and Related Dementias Research Ontology (CADRO) to classify treatment targets and mechanisms of action. We review our annual pipeline reports for the past 5 years to provide longitudinal insight into clinical trials and drug development for …

The Wiring Logic Of Identified Serotonergic Neurons Across Olfactory Networks In Drosophila, Kaylynn E. Coates

Graduate Theses, Dissertations, and Problem Reports (ETD)

Serotonin is a ubiquitous neuromodulator that confers flexibility in networks to modulate a wide array of behavioral and physiological processes. However, due to the complexity and heterogeneity of serotonergic systems, it has been challenging to determine the patterns of connectivity as well as the physiological contexts that influence individual serotonin neurons. In this dissertation, I use two serotonergic neurons which innervate the Drosophila olfactory system, the CSDns, as a model to explore these broad questions comprehensively using anatomical approaches. I first show that the CSDns have distinct connectivity relationships with populations of antennal lobe principal olfactory neurons and that their …

Image And Video-Based Autism Spectrum Disorder Detection Via Deep Learning, Mindi Ruan

Graduate Theses, Dissertations, and Problem Reports (ETD)

People with Autism Spectrum Disorder (ASD) show atypical attention to social stimuli and aberrant gaze when viewing images of the physical world. However, it is unknown how they perceive the world from a first-person perspective. In this study, we used machine learning to classify photos taken in three different categories (people, indoors, and outdoors) as either having been taken by individuals with ASD or by peers without ASD. Our classifier effectively discriminated photos from all three categories but was particularly successful at classifying photos of people with >80% accuracy. Importantly, the visualization of our model revealed critical features that led …

Cerebrovascular Dysfunction And Degeneration In Alzheimer’S Disease Pathophysiology, Dominic Dimitri Quintana

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a terminal illness and the most common form of dementia, which disproportionately affects the aged population. The pathophysiology of AD is characterized by neurodegeneration that slowly progresses, affecting regions of the brain that are involved in learning, memory, language, and executive function. In patients with the disease, early symptoms include non-disruptive forgetfulness that evolves into the inability to form new memories and ultimately the loss of autonomy at late stages. Histopathological hallmarks in the brain from patients with AD is the presence of amyloid-β (Aβ)-plaques and neurofibrillary tangles (NFT) deposited in the parenchyma. Since the discovery …

A Flight Sensory-Motor To Olfactory Histamine Circuit Mediates Olfactory Processing Of Ecologically And Behaviorally Natural Stimuli, Samual P. Bradley

Graduate Theses, Dissertations, and Problem Reports (ETD)

Environmental pressures have conferred species specific behavioral and morphological traits to optimize reproductive success. To optimally interact with their environment, nervous systems have evolved motor-to-sensory circuits that mediate the processing of its own reafference. Moth flight behavioral patterns to odor sources are stereotyped, presumably to optimize the likelihood of interacting with the odor source. In the moth Manduca sexta wing beating causes oscillatory flow of air over the antenna; because of this, odorant-antennal interactions are oscillatory in nature. Electroantennogram recordings on antennae show that the biophysical properties of their spiking activity can effectively track odors presented at the wing beat …

Neuroimaging Of Real-World Audio-Visual Sensory Integration In High-Functioning Autism, Paula J. Webster

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sensory processing differences are a prevalent aspect of autism spectrum disorder (ASD) that may contribute to core deficits of ASD such as repetitive behaviors as well as comorbidities including anxiety disorders. The ability to integrate information among our senses is required to comprehend the world around us and is crucial for the development of language, motor skills, and social communication. Prior studies have shown that individuals with autism differ from individuals without autism when presented with simple, non-natural audio-visual stimuli such as basic shapes accompanied by pure tones. Because the human brain processes non-natural and natural stimuli differently, more recent …

Automated And Standardized Tools For Realistic, Generic Musculoskeletal Model Development, Trevor Rees Moon

Graduate Theses, Dissertations, and Problem Reports (ETD)

Human movement is an instinctive yet challenging task that involves complex interactions between the neuromusculoskeletal system and its interaction with the surrounding environment. One key obstacle in the understanding of human locomotion is the availability and validity of experimental data or computational models. Corresponding measurements describing the relationships of the nervous and musculoskeletal systems and their dynamics are highly variable. Likewise, computational models and musculoskeletal models in particular are vitally dependent on these measurements to define model behavior and mechanics. These measurements are often sparse and disparate due to unsystematic data collection containing variable methodologies and reporting conventions. To date, …

Retrospective Unbiased Plasma Lipidomic Of Progressive Multiple Sclerosis Patients-Identifies Lipids Discriminating Those With Faster Clinical Deterioration, Mario Amatruda, Maria Petracca, Maureen Wentling, Benjamin Inbar, Kamilah Castro, Emily Y. Chen, Michael A. Kiebish, Keith Edwards, Matilde Inglese, Patrizia Casaccia

Advanced Science Research Center

The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the …

Divalent Metal Cation Entry And Cytotoxicity In Jurkat T Cells: Role Of Trpm7 Channels, Alayna N. Mellott

Browse all Theses and Dissertations

Humans are exposed daily to a variety of metals that can be harmful to our immune system. Although certain divalent metal cations are essential for numerous cellular functions and are critical trace elements in humans, the uptake mechanisms of these ions remain mostly unknown. Transient receptor potential melastatin 7 (TRPM7), which is expressed in a variety of human cell types, including lymphocytes and macrophages, conducts many divalent metal cations. TRPM7 channels are largely inactive under normal physiological conditions due to cytoplasmic magnesium acting as a channel inhibitor. Magnesium is a cofactor for many biochemical reactions. Low serum levels of magnesium, …

Barrels Xxxii Meeting Report: Whiskers In The Windy City, Giuseppe Cataldo, Chia-Chien Chen, Alicia C. Barrientos, Joshua C. Brumberg

Publications and Research

The 32^nd Annual Barrels meeting was hosted at the Northwestern University Feinberg School of Medicine in Chicago, Illinois on October 17^th and 18^th, 2019. The annual meeting brings together researchers who utilize the rodent whisker-to-barrel system as a means to understand cortical function and development. This year’s meeting focused on social behaviors, development and cerebellar functions within the barrel system and beyond.