Medicine and Health Sciences Commons^™

Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen

Dissertations (1934 -)

Glutamatergic signaling is fundamental to human behavior and its dysfunction is implicated in a wide range of neurological and neurodegenerative disorders. Excitatory amino-acid transporters (EAATs) – of which four primary subtypes (EAAT1, EAAT2, EAAT3, and EAAT4) exist in the human brain – are primary regulators of glutamate signaling. Endogenously-expressed at either low (EAAT4-low) or high (EAAT4-high) concentration in cerebellar Purkinje cells, EAAT4 has been shown to regulate Purkinje cell activity in the cerebellar molecular layer. However, differences in glutamatergic signaling at the circuit and single-synaptic levels in EAAT4-low and EAAT4-high regions are poorly understood. To characterize EAAT4-specific effects on excitatory …

Pseudotumoral Hemicerebellitis In A Young Male Sailor With Complete Recovery After Steroid Therapy, Khizer Masroor Anns, Faheem Ullah Khan, Muhammad Aman, Anwar Ahmad, Kumail Khandwala, Zainab Aslam Saeed Memon, Izaz Ahmad, Muhammad Ismail Safi

Medical College Documents

Pseudotumoral hemicerebellitis is a rare presentation of acute cerebellitis, which involves the inflammation of a single cerebellar hemisphere and most commonly affects children. It mimics a tumor on imaging, hence given the name. In this report, we present a case of pseudotumoral hemicerebellitis in a 30-year-old male who presented to the emergency room (ER) with complaints of vertigo, vomiting, and a headache.

Cerebellar Interneurons Control Fear Memory Consolidation Via Learning-Induced Hcn Plasticity, Kathryn Lynn Carzoli, Georgios Kogias, Jessica Fawcett-Patel, Si-Qiong J. Liu

School of Medicine Faculty Publications

While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation. The fear conditioning paradigm produces a lasting reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in these interneurons. This change increases intrinsic membrane excitability and enhances the response to synaptic stimuli. HCN loss is driven …

Identifying The Neural Correlates Of Anticipatory Postural Control: A Novel Fmri Paradigm, Jo Armour Smith, Rongwen Tain, Kelli G Sharp, Laura M Glynn, Linda R Van Dillen, Korinne Henslee, Jesse V Jacobs, Steven C Cramer

2020-Current year OA Pubs

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the …

Neuroinflammation, Oxidative Stress, Apoptosis, Microgliosis And Astrogliosis In The Cerebellum Of Mice Chronically Exposed To Waterpipe Smoke, Naserddine Hamadi, Sumaya Beegam, Nur Elena Zaaba, Ozaz Elzaki, Mariam Abdulla Altamimi, Abderrahim Nemmar

All Works

Waterpipe smoking (WPS) is prevalent in Asian and Middle Eastern countries and has recently gained worldwide popularity, especially among youth. WPS has potentially harmful chemicals and is associated with a wide range of adverse effects on different organs. However, little is known regarding the impact of WPS inhalation on the brain and especially on the cerebellum. Presently, we aimed at investigating inflammation, oxidative stress and apoptosis as well as microgliosis and astrogliosis in the cerebellum of BALB/C mice chronically (6 months) exposed to WPS compared with air-exposed mice (control). WPS inhalation augmented the concentrations of proinflammatory cytokines tumor necrosis factor, …

Explicit And Implicit Emotion Processing In The Cerebellum: A Meta‑Analysis And Systematic Review, Jordan E. Pierce, Marine Thomasson, Philippe Voruz, Garance Selosse, Julie Péron

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

The cerebellum’s role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified …

The Neuroprotective Effects Of Estradiol And Genistein In Zebra Finch Cerebellum, Renee E. Breaux

Honors Theses

The estradiol (E2) synthetic pathway converts testosterone to E2 via aromatase (AROM) and plays an important role in neuroplasticity. However, exogenous E2 increases cancer risk and interferes with gonadal function. Phytoestrogens, plant-based estrogens, may provide neuroprotection without negative E2 effects. Genistein (GEN), a soy phytoestrogen, preferentially binds to estrogen receptor beta (ER β), which is expressed at a relatively higher concentration than ER α in the cerebellum (CB). The songbird CB is an ideal model for steroid-mediated plasticity. Songbird brains are highly plastic and CB contains all steroid-synthetic enzymes. Previous studies in zebra finches (ZF) have shown that AROM and …

Isolation And Recording Of Thalamic Neuronal Activity From Ventral Medial And Ventral Lateral Thalamic Nuclei In Rat, Michael Bien, Halley Fowler, Jessica Hiscox, Anum Ul-Haque, Huo Lu

Research Day

The cerebellum, known for its role in coordination and motor adaptation, is hypothesized to travel through the thalamus in its signaling to and from the cerebral cortex, specifically through the ventral medial (VM) and ventral lateral (VL) thalamic nuclei. The thalamus is located within the diencephalon between the midbrain and cerebral cortex. It is an important relay center between the cerebellum and the motor cortex.

Isolation and recording of electrical activity from neurons in the ventral medial and ventral lateral thalamic nuclei in rats is the first step to study the thalamic response to electrical cerebellar stimulation in future experiments. …

The Social Cerebellum: A Large-Scale Investigation Of Functional And Structural Specificity And Connectivity, Athanasia Metoki, Yin Wang, Ingrid R Olson

2020-Current year OA Pubs

The cerebellum has been traditionally disregarded in relation to nonmotor functions, but recent findings indicate it may be involved in language, affective processing, and social functions. Mentalizing, or Theory of Mind (ToM), is the ability to infer mental states of others and this skill relies on a distributed network of brain regions. Here, we leveraged large-scale multimodal neuroimaging data to elucidate the structural and functional role of the cerebellum in mentalizing. We used functional activations to determine whether the cerebellum has a domain-general or domain-specific functional role, and effective connectivity and probabilistic tractography to map the cerebello-cerebral mentalizing network. We …

Cerebellum-Seeded Functional Connectivity Changes In Trait-Anxious Individuals Undergoing Attention Bias Modification Training, Katherine Elwell

All NMU Master's Theses

Anxiety and anxiety related disorders are increasing at a drastic rate in the past decade, with the NIMH reporting that 31.1% of U.S. adults will experience an anxiety disorder at some point in their lives. Anxiety is commonly characterized by increased attention bias to threat. Attention Bias Modification (ABM) is a new treatment used to reduce individual’s attention bias towards threat. The extent to which ABM leads to underlying neural changes is still unknown. The cerebellum is a neglected brain structure, with new research provides evidence that cerebellum’s functional connectivity and shared networks with threat processing regions has a direct …

The Cerebellum's Relationship To Language Function Following Perinatal Stroke, Carolina Alexis Vias

FIU Electronic Theses and Dissertations

While recent studies have demonstrated the association between the cerebellum and higher-order cognitive functioning, it is still unclear how volumetric differences of specific regions of interests within the cerebellum across typical and atypical development are related to language function. We have done so by measuring the volume of cerebellar subregions of healthy controls, and compared the volume to behavioral measures of language function. We then followed with an analysis of the cerebellum’s relationship to language function following perinatal stroke, which provides us with a greater knowledge of the impact of a cortical injury on cerebellar development and the cognitive outcomes …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Using The Schmahmann Syndrome Scale To Assess Cognitive Impairment In Young Adults With Metabolic Syndrome: A Hypothesis-Generating Report, Eithan Kotkowski, Larry R. Price, Cheasequah J. Blevins, Crystal Franklin, Mary Woolsey, Ralph A. Defronzo, John Blangero, Ravindranath Duggirala, David C. Glahn, Jeremy Schmahmann, Peter T. Fox

School of Medicine Publications and Presentations

The posterior cerebellum is the most significantly compromised brain structure in individuals with metabolic syndrome (MetS) (Kotkowski et al., 2019). In light of this, we hypothesized that cognitive decline reported in patients with MetS is likely related to posterior cerebellar atrophy. In this study, we performed a post-hoc analyses using T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) in the form of voxel-wise tract-based spatial statistics (TBSS), biometric, and psychometric data from young participants with (n = 52, aged 18–35 years) and without MetS (n = 52, aged 18–35 years). To test the predictive value of components …

Downbeat Nystagmus In A 7-Year-Old Girl With Epstein-Barr Virus-Associated Meningitis And Cerebellitis, Cameron A. Wade, David Neil Toupin, Kyle Darpel, Kimberly S. Jones, Donita D. Lightner

Neurology Faculty Publications

Downbeat nystagmus is a type of jerk nystagmus that may be seen in patients with lesions affecting the vestibulocerebellum. This is a case of a 7-year-old girl presenting with a history of fever, headache, and episodic vertigo with downbeat nystagmus. The diagnosis of Epstein-Barr virus meningitis with acute cerebellitis was made by contrast magnetic resonance imaging, cerebrospinal fluid analysis, and serum Epstein-Barr virus titers. Contrast magnetic resonance imaging demonstrated enhancement of the meninges and inferior cerebellar folia, correlating with the neuroophthalmological symptom of downbeat nystagmus.

Fronto-Cerebellar Connectivity Mediating Cognitive Processing Speed, Clive H Y Wong, Jiao Liu, Tatia M C Lee, Jing Tao, Alex W K Wong, Bolton K H Chau, Lidian Chen, Chetwyn C H Chan

2020-Current year OA Pubs

Processing speed is an important construct in understanding cognition. This study was aimed to control task specificity for understanding the neural mechanisms underlying cognitive processing speed. Forty young adult subjects performed attention tasks of two modalities (auditory and visual) and two levels of task rules (compatible and incompatible). Block-design fMRI captured BOLD signals during the tasks. Thirteen regions of interest were defined with reference to publicly available activation maps for processing speed tasks. Cognitive speed was derived from task reaction times, which yielded six sets of connectivity measures. Mixed-effect LASSO regression revealed six significant paths suggestive of a cerebello-frontal network …

Systems Genetics And Systems Biology Analysis Of Paraquat Effects In Bxd Recombinant Inbred Mice, Carolina Del Valle Torres Rojas

Theses and Dissertations (ETD)

Paraquat (PQ) is a chemical herbicide that is used in many countries including the United States. It is also highly acutely toxic to humans and has been used as a means of suicide. As PQ is applied mainly in agricultural settings, it moves to soil and well water. Chronic low dose exposure via drinking water may have adverse effects on humans, including increased risk for sporadic Parkinson’s disease (sPD). The etiology of sPD is unclear and the most accepted hypothesis states it is the result of the interaction between environmental factors and genetic susceptibility. Increasing evidence led us to infer …

Central Nervous System Pathology In Preclinical Mps Iiib Dogs Reveals Progressive Changes In Clinically Relevant Brain Regions, Martin T Egeland, Marta M Tarczyluk-Wells, Melissa M Asmar, Evan G Adintori, Roger Lawrence, Elizabeth M Snella, Jackie K Jens, Brett E Crawford, Jill C M Wait, Emma Mccullagh, Jason Pinkstaff, Jonathan D Cooper, N Matthew Ellinwood

2020-Current year OA Pubs

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B) is an autosomal recessive lysosomal storage disorder caused by the deficiency of alpha-N-acetylglucosaminidase activity, leading to increased levels of nondegraded heparan sulfate (HS). A mouse model has been useful to evaluate novel treatments for MPS IIIB, but has limitations. In this study, we evaluated the naturally occurring canine model of MPS IIIB for the onset and progression of biochemical and neuropathological changes during the preclinical stages (onset approximately 24-30 months of age) of canine MPS IIIB disease. Even by 1 month of age, MPS IIIB dogs had elevated HS levels in brain …

Conditional Loss Of Engrailed 1/2 In Rhombic Lip-Derived Neurons Increases Intrinsic Rhythmicity And Decreases Overall Variability Of Eupneic Respiration, Angela P. Taylor

Theses and Dissertations (ETD)

Evidence for a cerebellar role during cardiopulmonary challenges has long been established, but investigation into cerebellar involvement in eupneic breathing has been inconclusive. Given the view of the cerebellum (CRB) as a temporally coordinating structure, any investigation into the CRB during respiration must evaluate rhythm and variability of the respiratory sequence. In this study, we chose an elegant model of cerebellar neuropathology, Atoh1-En1/2 CKO, where mutant animals have conditional loss of the developmental patterning gene Engrailed 1/2 in rhombic lip-lineage neurons and exhibit a proportional scaling-down of neuron number in hypoplastic lobules of the CRB. We utilized whole-body unrestrained plethysmography …

The Influence Of Cerebellar Transcranial Direct Current Stimulation On Motor Function In Parkinson’S Disease, Lidio Lima De Albuquerque

UNLV Theses, Dissertations, Professional Papers, and Capstones

Parkinson's disease (PD) is the most common movement disorder and the second most common neurodegenerative disorder. PD is characterized by dopaminergic cell loss in the substantia nigra pars compacta, which leads to a reduction in dopamine in the striatum. These physiological mechanisms lead to a number of motor impairments such as bradykinesia, rigidity, tremor, and postural instability that severely limit the ability of individuals with PD to perform many essential daily living activities. Although current pharmacological, surgical, and physical exercise treatment approaches are valuable they are either only mildly effective, expensive, or associated with a variety of side effects. Therefore, …

Improving The Assessment And Understanding Of Neurogenic Orthostatic Hypotension, Jacquie Baker

Electronic Thesis and Dissertation Repository

Neurogenic Orthostatic Hypotension (NOH) is a cardinal feature of autonomic failure. Patients with NOH experience a persistent and consistent drop in blood pressure when standing due to failure of the autonomic nervous system to reflexively increase sympathetic outflow. NOH affects individuals worldwide, presenting as both a primary feature (i.e. Multiple Systems Atrophy, Pure Autonomic Failure) and secondary to several common disorders including diabetes and Parkinson’s Disease. However, there are still several gaps in our overall understanding and assessment of patients with NOH. Therefore, the six studies presented in this thesis aimed to address some of these gaps in our current …

Assessment Of Motor Function, Motor Learning, & Olivary Climbing Fiber Distribution Within Developmental Hyperserotonemia Rat Model For Autism Spectrum Disorder, Elizabeth Diane Holland

MSU Graduate Theses

While Autism Spectrum Disorder (ASD) is defined by deficits in social communication, compromised motor function and motor learning have been increasingly reported. Motor deficits could compound social impairment through delayed language acquisition, reduced opportunity for social interaction, and affected nonverbal communication. One area of interest in the investigation of motor dysfunction is the cerebellum, where altered cerebellar structure and connectivity have been reported in those diagnosed with ASD. Morphological and functional changes in cerebellar circuitry could disrupt motor skill development and may be associated with developmental alterations of the serotonergic system. Elevated blood serotonin in perinatal development, developmental hyperserotonemia (DHS), …

Network Influence Of The Cerebellum For Predicting Dbs Response In Patients With Advanced Parkinson’S Disease, Lucy Li, Jennifer Muller, Sara Thalheimer, Mackenzie D. Silverman, Mahdi Alizadeh, Tsao-Wei Liang, Kelly Layton, Daniel Kremens, Victor Romo, Feroze Mohamed, Chengyuan Wu

Phase 1

Introduction: Deep brain stimulation (DBS) is a treatment option for reducing motor symptoms in patients with Parkinson’s Disease (PD) when first-line medication becomes ineffective. Existing literature has hypothesized that the clinical outcome of DBS may depend on brain connectivity profiles of the stimulation site to distant brain regions. However, the potential of brain connectivity profiles to predict response to DBS in PD remains unclear.

Objective: This study aimed to investigate how changes in structural and functional connectivity may relate to patient response to DBS, through the examination of brain network changes using graph theory.

Methods: Ten patients with advanced PD …

Static And Dynamic Postural Control Deficits In Aging Fragile X Mental Retardation 1 (Fmr1) Gene Premutation Carriers., Zheng Wang, Pravin Khemani, Lauren M Schmitt, Su Lui, Matthew W Mosconi

Articles, Abstracts, and Reports

BACKGROUND: Individuals with premutation alleles of the fragile X mental retardation 1 (FMR1) gene are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS) during aging. Characterization of motor issues associated with aging in FMR1 premutation carriers is needed to determine neurodegenerative processes and establish new biobehavioral indicators to help identify individuals at greatest risk of developing FXTAS.

METHODS: We examined postural stability in 18 premutation carriers ages 46-77 years and 14 age-matched healthy controls. Participants completed a test of static stance and two tests of dynamic postural sway on a force platform to quantify postural variability and complexity. CGG …

Dysregulation In The Central Nervous System Upon Mcmv Infection In Newborn Mice, Cathy Yea Won Sung

All ETDs from UAB

Human cytomegalovirus (HCMV) infection is a major cause of morbidity in infants and children throughout the world. Between 0.2-1.2% of all live births is infected with HCMV in the United States. Approximately 5-15% of these newborn babies will develop long-term neurological damage resulting in motor disorders, mental retardation, and sensorineural hearing loss. Although the neurological sequelae associated with congenital HCMV infections are well characterized, little is known about the pathogenesis of the damage to the central nervous system (CNS). To study the pathogenesis of congenital HCMV infection, we have developed a mouse model in which newborn mice are infected intraperitoneally …

Differential Expression Of Genes Related To Innate Immune Responses In Ex Vivo Spinal Cord And Cerebellar Slice Cultures Infected With West Nile Virus, Amber M. Paul, Parminder J.S. Vig, Deyin Lu, Ram Kuwar, Maria Lopez, Dobrivoje S. Stokic, A. Arturo Leis, Michael R. Garrett, Fengwei Bai

Publications

West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV …

Freezing Of Gait: Mechanisms, Mechanics, And Management, Peter S. Myers

Arts & Sciences Electronic Theses and Dissertations

Parkinson disease (PD) is a neurodegenerative disease with multiple motor and non-motor symptoms, including postural instability, gait impairments, and cognitive deficits. More than 50% of individuals with PD experience a symptom called freezing of gait (FOG), described as a transient inability to take another step forward. Individuals with PD who experience FOG (freezers) have further postural, gait, and cognitive impairments compared to individuals with PD without FOG (non-freezers). While degeneration of the dopaminergic neurons in the substantia nigra is accepted as the primary etiology of the disease, research shows that the disease has a global impact on the brain, accounting …

Shotgun Proteomics Analysis Of Protein Responding To Methamphetamine Addiction In Rat Cerebellum, Oranee Ritsayong, Sri-Arun Iamjan, Sittiruk Roytrakul, Samur Thanoi, Sutisa Nudmamud-Thanoi

Chulalongkorn Medical Journal

Background : Methamphetamine (METH) is an addictive psychostimulant drug that induces damages several regions of the brain, including the cerebellum. METH can induce some proteins changes in synaptic neurotransmission and signal transduction underlying the mechanism of drug addiction in several brain regions such as the striatum, hippocampus and nucleus accumbens. Nevertheless, few studies have examined the effects of METH in the cerebellum.Objective : The aim of the current study was to investigate changes in the synaptic neurotransmission and signal transduction protein expression in rat cerebellum following METH exposure using proteomics technique.Methods : Male Sprague-Dawley rats were treated with an escalating …

Sleep, And Its Relation To Non-Motor Deficits In Patients With Cerebellar Ataxia, Akshata Sonni

Doctoral Dissertations

The cerebellum is a highly connected structure, and its involvement in sleep – which is a dynamic process that is modulated by a complex set of neural systems – can come about through a number of neural pathways. We conducted two studies aimed at furthering our understanding of cerebellar involvement in sleep behavior and physiology, as well as measuring the impact of poor sleep on mood and cognition in patients with cerebellar degeneration. First, by means of an online battery including measures of sleep and neuropsychiatric function, we collected data from 176 patients with cerebellar ataxia. We found strong evidence …

Nutrient Intake In The First Two Weeks Of Life And Brain Growth In Preterm Neonates., Juliane Schneider, Céline J Fischer Fumeaux, Emma G Duerden, Ting Guo, Justin Foong, Myriam Bickle Graz, Patric Hagmann, M Mallar Chakravarty, Petra S Hüppi, Lydie Beauport, Anita C Truttmann, Steven P Miller

Brain and Mind Institute Researchers' Publications

BACKGROUND: Optimizing early nutritional intake in preterm neonates may promote brain health and neurodevelopment through enhanced brain maturation. Our objectives were (1) to determine the association of energy and macronutrient intake in the first 2 weeks of life with regional and total brain growth and white matter (WM) maturation, assessed by 3 serial MRI scans in preterm neonates; (2) to examine how critical illness modifies this association; and (3) to investigate the relationship with neurodevelopmental outcomes.

METHODS: Forty-nine preterm neonates (21 boys, median [interquartile range] gestational age: 27.6 [2.3] weeks) were scanned serially at the following median postmenstrual weeks: 29.4, …