Neurosciences Commons^™

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E. Irmen, Nicholas J. Constantino, Chanung Wang, Michael F. Kanan, Marco Colonna, Shannon L. Macauley, Jocelyn Y. Cheng, Ken Hatanaka, Margaret Moline, Erik S. Musiek

Sanders-Brown Center on Aging Faculty Publications

Background: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer’s disease (AD). The orexin/hypocretin system regulates sleep–wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

Methods: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …

Intranasal Delivery Of Extracellular Vesicles Derived From Human Bone Marrow Mesenchymal Stem Cells Dampens Neuroinflammation And Ameliorates Motor Deficits In A Mouse Model Of Cortical Stroke, Saviana Antonella Barbati, Chiara D'Amelio, Chiara Feroleto, Marta Morotti, Ida Nifo Sarrapochiello, Francesca Natale, Domenica Donatella Li Puma, Yolanda Gomez-Galvez, Elena Blanco-Suarez, Lorraine Iacovitti, Lucia Leone, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi

Department of Neuroscience Faculty Papers

Early treatment of ischemic stroke can significantly reduce disability and mortality rates. Stem cell-derived extracellular vesicles (EVs) have shown potential as therapeutics for neurological disorders. This study explored whether intranasal administration of EVs from human bone marrow mesenchymal stem cells (BM-MSCs) enhances forelimb motor function recovery in a mouse model of motor cortex stroke and investigated their mechanism of action, focusing on neuroinflammation. C57BL/6JRj mice received EV treatment of 0.1 × 10⁹ EVs per dose per day, 48 h post-stroke and twice weekly for four weeks. EV-treated mice showed significant improvement in forelimb deficits, as evaluated using a series …

Microglia Sensing Of Peripheral Signals That Bridge The Brain And Body, Claire E Young, Melanie A Samuel

Faculty, Staff and Students Publications

Microglia are the resident immune cell of the brain, and alterations in microglia signaling have been implicated in many neurodegenerative disorders. While microglia responses to central cues and other brain cell types are well documented, studies are increasingly investigating the impact of peripherally derived signals on microglia function. A diverse array of peripheral cues, including dietary components, hormones, and bacteria metabolites and components from the microbiome cross the blood brain barrier and directly influence microglia state through ligand-receptor interactions. This review highlights the complexity of brain-body interactions from the perspective of microglia function and proposes the idea that microglia could …

Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response In Aged And Young Tbi Mouse Models, Salma S. Abdelmaboud

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and …

Transcriptomic And Epigenomic Profiling Of Immune Cells Responses To Simian Immunodeficiency Virus Infection In The Brain, Xiaoke Xu

Theses & Dissertations

Human immunodeficiency virus type 1 (HIV-1) is an enveloped retrovirus that significantly impairs the human immune system. A common complication of HIV-1 infection is HIV-associated neurocognitive disorder (HAND), which, prior to the introduction of antiretroviral therapy (ART), led to considerable morbidity and mortality due to untreated neuropsychiatric manifestations. Although ART has substantially reduced the incidence of HIV-associated dementia (HAD), approximately 50% of people living with HIV (PLWH) continue to experience milder forms of HAND. The CNS is seeded by HIV during the acute phase of infection. Once in the brain, HIV targets and activates resident immune cells, primarily microglia and …

Retinal Ganglion Cell Migration And Viability Requires The Kinase Lkb1, Robert D Mackin, Ritika V Bhalla, Viktor Akhanov, Qudrat T Abdulwahab, Courtney A Burger, Melanie A Samuel

Faculty, Staff and Students Publications

The arrangement of neurons into ordered layers underlies circuit function in many nervous system regions. This is particularly true in the mammalian retina. Here, fate-committed retinal ganglion cells (RGCs) migrate from the apical to the inner retina, where they form connections that enable vision. The mechanisms that permit ganglion cell migration and whether distinct ganglion cell types use different migration modes are unknown. We show that the serine/threonine kinase LKB1 regulates ganglion cell migration and nuclear positioning. In the absence of LKB1, many ganglion cells remain in the apical retina. Misplaced cells show modified morphologies and display altered cytoskeletal proteins. …

The Therapeutic Potential Of Butyrate And Lauric Acid In Modulating Glial And Neuronal Activity In Alzheimer’S Disease, Rathnayaka Mudiyanselage Uththara Sachinthanie Senarath, Lotta E. Oikari, Prashant Bharadwaj, Vijay Jayasena, Ralph N. Martins, Wanakulasuriya Mary Ann Dipika Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen species (ROS), while astrocytes undergo reactive astrogliosis, further impairing neuronal health. This maladaptive response from glial cells significantly accelerates disease pathology. Current AD treatments primarily aim …

Anxiolytic Intervention: Modulation Of Cell Types Due To Nicotine Withdrawal, Taylor Elder

Theses and Dissertations--Pharmacy

Nicotine use disorder (NUD) remains a leading cause of preventable disease, yet the neurobiological mechanisms underlying nicotine withdrawal are incompletely understood. Emerging evidence implicates neuroimmune signaling and astrocytic regulation of glutamate in shaping the withdrawal-associated affective phenotype. This dissertation investigated these processes using multiple nicotine administration paradigms including osmotic minipump implant, cigarette smoke exposure, and nicotine vapor inhalation to model diverse routes of human nicotine intake.

Chapter 2 examines the effects of these three modes of administration on neuroinflammation and validation of nicotine delivery. Nicotine exposure was confirmed through receptor [³H]Epibatidine nAChR binding assay and serum cotinine measurements. …

Retinal Ganglion Cell Circuits And Glial Interactions In Humans And Mice, Kang-Chieh Huang, Mohamed Tawfik, Melanie A Samuel

Faculty, Staff and Students Publications

Retinal ganglion cells (RGCs) are the brain's gateway for vision, and their degeneration underlies several blinding diseases. RGCs interact with other neuronal cell types, microglia, and astrocytes in the retina and in the brain. Much knowledge has been gained about RGCs and glia from mice and other model organisms, often with the assumption that certain aspects of their biology may be conserved in humans. However, RGCs vary considerably between species, which could affect how they interact with their neuronal and glial partners. This review details which RGC and glial features are conserved between mice, humans, and primates, and which differ. …

Neuroprotective Effect Of L-Dopa-Induced Interleukin-13 On Striatonigral Degeneration In Cerebral Ischemia, Eunhae Jeon, Myeong-Seong Seo, Enkhmaa Lkhagva-Yondon, Yu-Ree Lim, Seung-Woo Kim, Yu Jeong Kang, Jun Seok Lee, Byoung Dae Lee, Rayul Wi, So-Yoon Won, Young Cheul Chung, Eun S Park, Eunhee Kim, Byung Kwan Jin, Myung-Shin Jeon

Faculty, Staff and Student Publications

Levodopa (L-DOPA) treatment is a clinically effective strategy for improving motor function in patients with ischemic stroke. However, the mechanisms by which modulating the dopamine system relieves the pathology of the ischemic brain remain unclear. Emerging evidence from an experimental mouse model of ischemic stroke, established by middle cerebral artery occlusion (MCAO), suggested that L-DOPA has the potential to modulate the inflammatory and immune response that occurs during a stroke. Here, we aimed to demonstrate the therapeutic effect of L-DOPA in regulating the systemic immune response and improving functional deficits in mice with ischemia. Transient MCAO led to progressive degeneration …

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

In Vivo Examination Of Peripheral Drivers Of Alzheimer’S Disease, Celso Catumbela

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and predominantly affects elderly populations. This disease is well known for its effects on the brain, but a wealth of clinical reports show that dementia can also modify, or be modified by, various peripheral and systemic processes. Yet, the pathological contribution of peripheral comorbidities to AD remains to be fully understood. In an attempt to address some knowledge gaps, we characterized the cerebral and peripheral pathology in mice with history of either liver injury or sepsis. In the former subjects, we found that even in the absence of genetic risk …

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …

The Mitochondrial Membrane Potential As A Screening Tool For Immunostimulation, Kendra Mcglothen

UNLV Theses, Dissertations, Professional Papers, and Capstones

The rise of neuroinflammatory disorders highlights the importance of early detection and intervention for more effective treatment options. Neuroinflammation is associated with the pathogenesis of many neurological disorders, including Major Depressive Disorder, Alzheimer's disease, and Multiple Sclerosis. There has been a focus on neurons to advance our understanding of the underlying mechanisms of neuroinflammation and its role in neurodegeneration. However, recent studies have highlighted the pivotal role of glial cells, particularly microglia, in neuroinflammation due to their active participation in the immune response. This study investigates glial-specific indicators of morphology, metabolic changes, and drug efficacy in neuroinflammatory conditions. By analyzing …

Interaction Of High-Fat Diet And Brain Trauma Alters Adipose Tissue Macrophages And Brain Microglia Associated With Exacerbated Cognitive Dysfunction, Rebecca J Henry, James P Barrett, Maria Vaida, Niaz Z Khan, Oleg Makarevich, Rodney M Ritzel, Alan I Faden, Bogdan A Stoica

Faculty, Staff and Student Publications

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular …

4r-Cembranoid Suppresses Glial Cells Inflammatory Phenotypes And Prevents Hippocampal Neuronal Loss In Lps-Treated Mice, Luis A Rojas-Colón, John B Redell, Pramod K Dash, Pedro E Vegas, Wanda Vélez-Torres

Faculty, Staff and Student Publications

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

Longitudinal Single-Cell Transcriptional Dynamics Throughout Neurodegeneration In Sca1, Leon Tejwani, Neal G Ravindra, Changwoo Lee, Yubao Cheng, Billy Nguyen, Kimberly Luttik, Luhan Ni, Shupei Zhang, Logan M Morrison, John Gionco, Yangfei Xiang, Jennifer Yoon, Hannah Ro, Fatema Haidery, Rosalie M Grijalva, Eunwoo Bae, Kristen Kim, Regina T Martuscello, Harry T Orr, Huda Y Zoghbi, Hayley S Mcloughlin, Laura P W Ranum, Vikram G Shakkottai, Phyllis L Faust, Siyuan Wang, David Van Dijk, Janghoo Lim

Duncan NRI Faculty and Staff Publications

Neurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately results in the death of vulnerable neuronal populations. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellar tissue, establishing continuous dynamic trajectories of each cell population. Importantly, we defined the precise transcriptional changes that precede loss of Purkinje cells and, for the first time, identified robust early transcriptional dysregulation in unipolar brush cells and oligodendroglia. Finally, we applied a …

Doxycycline For Transgene Control Disrupts Gut Microbiome Diversity Without Compromising Acute Neuroinflammatory Response, Emily J Koller, Caleb A Wood, Zoe Lai, Ella Borgenheimer, Kristi L Hoffman, Joanna L Jankowsky

Faculty, Staff and Students Publications

The tetracycline transactivator (tTA) system provides controllable transgene expression through oral administration of the broad-spectrum antibiotic doxycycline. Antibiotic treatment for transgene control in mouse models of disease might have undesirable systemic effects resulting from changes in the gut microbiome. Here we assessed the impact of doxycycline on gut microbiome diversity in a tTA-controlled model of Alzheimer's disease and then examined neuroimmune effects of these microbiome alterations following acute LPS challenge. We show that doxycycline decreased microbiome diversity in both transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite the change in microbiome composition, doxycycline treatment …

The Role Of Dystrophic Microglia In Aging And Disease, Ryan K. Shahidehpour

Theses and Dissertations--Neuroscience

Microglia are the primary immune cells of the central nervous system and are crucial in maintaining homeostasis and defense from disease and injury in the brain. Recent genome-wide association studies (GWAS) have also highlighted microglia as a central player in Alzheimer’s disease (AD). However, the mechanisms of microglia’s influence are poorly understood. Traditionally, microglial subtypes characterized physiologically as “reactive” or “activated” have been linked with disease and injury in the brain. However, morphologically, a recently described microglia category known as “dystrophic,” characterized structurally by fragmented processes and cytoplasmic decay is believed to be more strongly associated with aging and neurodegeneration. …

In Sickness And In Health-Type I Interferon And The Brain, Wei Cao

Faculty, Staff and Student Publications

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms …

Fornix Volumetric Increase During Aging Associates To Microglia Activation Leading To Defective Cognitive Performance, Marcela Cárdenas Tueme, Luis Ángel Trujillo-Villarreal, Victor Ramírez-Amaya, Eduardo Garza-Villarreal, Alberto Camacho-Morales, Diana Reséndez-Pérez

Research Symposium

Background: Ageing displays a low-grade pro-inflammatory profile in blood and brain. It has been documented proinflammatory cytokines accumulation leading to neuroinflammation during aging. Aged brains integrate pro inflammatory cytokines accumulation, active microglia and volumetric changes which correlates with defective cognitive performance and neurodegeneration.

Methods: Mice from 2-,12- and 20-months-old of age were submitted to different memory tests: Y-maze, Barnes maze, object location test and object location test. Afterwards, we performed structural MRI to evaluate macrostructural changes related to memory and learning regions. Following this, we also evaluated in peripheral blood and in brain tissue the presence of pro-inflammatory cytokines …

Complement C3ar Depletion Reverses Hif-1Α-Induced Metabolic Impairment And Enhances Microglial Response To Aβ Pathology, Manasee Gedam, Michele M Comerota, Nicholas E Propson, Tao Chen, Feng Jin, Meng C Wang, Hui Zheng

Faculty, Staff and Students Publications

Microglia are the major cell type expressing complement C3a receptor (C3aR) in the brain. Using a knockin mouse line in which a Td-tomato reporter is incorporated into the endogenous C3ar1 locus, we identified 2 major subpopulations of microglia with differential C3aR expression. Expressing the Td-tomato reporter on the APPNL-G-F-knockin (APP-KI) background revealed a significant shift of microglia to a high-C3aR-expressing subpopulation and they were enriched around amyloid β (Aβ) plaques. Transcriptomic analysis of C3aR-positive microglia documented dysfunctional metabolic signatures, including upregulation of hypoxia-inducible factor 1 (HIF-1) signaling and abnormal lipid metabolism in APP-KI mice compared with wild-type controls. Using primary …

Tmem106b Regulates Microglial Proliferation And Survival In Response To Demyelination, Tingting Zhang, Weilun Pang, Tuancheng Feng, Jennifer Guo, Kenton Wu, Mariela Nunez Santos, Akshayakeerthi Arthanarisami, Alissa L Nana, Quynh Nguyen, Peter J Kim, Joanna L Jankowsky, William W Seeley, Fenghua Hu

Faculty, Staff and Students Publications

TMEM106B, a lysosomal transmembrane protein, has been closely associated with brain health. Recently, an intriguing link between TMEM106B and brain inflammation has been discovered, but how TMEM106B regulates inflammation is unknown. Here, we report that TMEM106B deficiency in mice leads to reduced microglia proliferation and activation and increased microglial apoptosis in response to demyelination. We also found an increase in lysosomal pH and a decrease in lysosomal enzyme activities in TMEM106B-deficient microglia. Furthermore, TMEM106B loss results in a significant decrease in the protein levels of TREM2, an innate immune receptor essential for microglia survival and activation. Specific ablation of TMEM106B …

Bioinformatic Analysis Predicts Microglial Dysfunction In Murine Aging, Amadu Idrisa Jalloh

USF Tampa Graduate Theses and Dissertations

Age-related disease is a growing concern as the global geriatric population increases. Neurodegenerative diseases scale unfavorably in prevalence with aging and inflict disastrous consequences to human health and well-being. These disorders are challenging to investigate because they arise from complex molecular origins. The neuroimmune system is a common factor among these diseases and microglia play an important role in maintaining homeostasis in the central nervous system. Aging progressively impairs microglia by decreasing their ability to adapt and respond to noxious environmental stimuli or injury. Microglial dysfunction aggravates neurodegenerative pathology when microglia are unable to regulate neuroinflammation effectively. We investigated aging …

Intravital Imaging Of Cellular Response Due To Traumatic Brain Injury Using Confocal Microscopy, Enoch G. Kim, Jeffrey Horbatiuk, Carolyn Harris

Medical Student Research Symposium

Introduction: Cellular reaction to traumatic brain injury is complex and involves considerable interactions between cells and reactivity to foreign bodies. Our objective was to assess neurons, microglia, astrocytes, and intracellular Ca²⁺ signaling by creating a novel confocal microscopy technique involving an air immersed lens that does not sacrifice resolution and limits signal attenuation. This study aimed to create a consistent dynamic methodology to observe the cortical cellular response using real-time intravital imaging as trauma is being induced.

Methods: Once surgical plane was achieved, rodent cortices were exposed via craniotomy and blunt insertion with a silicone shunt catheter into the …

Massive Loss Of Proprioceptive Ia Synapses In Rat Spinal Motoneurons After Nerve Crush Injuries In The Postnatal Period, Ariadna Arbat-Plana, Sara Bolívar, Xavier Navarro, Esther Udina, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries (PNIs) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from α-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed, and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. The goal of this study was to analyze …

Glial Cell-Specific Contribution Of Pkr-Like Er Kinase (Perk) In Neuroinflammation And Behavior, Anirudhya Lahiri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological disorders such as multiple sclerosis (MS) are a major public health concern in the US, with no available therapeutic cure. Chronic neuroinflammation and aberrant proteostasis in the central nervous system (CNS) are the major hallmarks of neurological diseases. Endoplasmic Reticulum (ER) is a major cellular organelle involved in protein synthesis, folding and maturation of various secretory and transmembrane proteins. Pathophysiological stressors such as trauma and infection result in misfolded protein accumulation in the endoplasmic reticulum (ER) lumen, which results in ER stress. To regain proteostasis (protein homeostasis), cells activate the unfolded protein response (UPR). UPR is an evolutionarily conserved …

Genetic Expression Changes And Pathologic Findings Associated With Hyperhomocysteinemia In Human Autopsy Brain Tissue, Erica M. Weekman, Zachary Winder, Colin B. Rogers, Erin L. Abner, Tiffany L. Sudduth, Ela Patel, Adam J. Dugan, Shuling X. Fister, Brandi Wasek, Peter T. Nelson, Gregory A. Jicha, Teodoro Bottiglieri, David W. Fardo, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking.

Methods: A subset of research volunteers from the University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort came to autopsy and had ante mortem plasma homocysteine levels available. Brain tissue and blood plasma drawn closest to death were used to measure …