Neurology Commons^™

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …

Utilizing Ai Integrated Neuroimaging Technology To Expand Upon Machine Learning In Positron Emission Tomography Technology With The Aim Of Detecting Amyloid Beta Biomarkers Early In The Onset Of Alzheimer's., Ethan S. Terman

Undergraduate Research Posters

Early intervention in Alzheimer's is vital for treatment. The earlier a professional can detect symptoms and make a diagnosis the earlier a prognosis can be implemented. With the prevalence of data in our day-to-day world combined with Artificial intelligence (AI), utilizing both for machine learning can pave the way for more accurate and efficient detection of Alzheimer's and other neurodegenerative diseases. AI combined with Machine learning (ML) increases diagnostic efficiency and reduces human errors, making it a valuable resource for physicians and clinicians alike. With the increasing amount of data processing and image interpretation required, the ability to use AI …

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …

A Blunted Th17 Cytokine Signature In Women With Mild Cognitive Impairment: Insights From Inflammatory Profiling Of A Community-Based Cohort Of Older Adults, Adam D. Bachstetter, Jenny Lutshumba, Edric D. Winford, Erin L. Abner, Barbra J. Martin, Jordan P. Harp, Linda J. Van Eldik, Frederick A. Schmitt, Donna M. Wilcock, Ann M. Stowe, Gregory A. Jicha, Barbara S. Nikolajczyk

Markey Cancer Center Faculty Publications

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

Palmitoylation As A Regulator Of Maguk Proteins Postsynaptic Localization, Rozena Shirvani-Arani, Santiago Balderas, Yonghong Zhang, Xioaqian Fang

Research Symposium

Synaptic plasticity is the ability of the brain to make changes and the changes occur at synapses. To achieve the complicated functions, a good number of proteins are present at synapse and are called synaptic proteins. To stabilize these proteins at synapses, proteins are modified through posttranslational modifications (PTMs). The most studied PTMs include phosphorylation, acetylation, ubiquitination, glycosylation, palmitoylation, etc. Palmitoylation is a type of lipid modification and has received more attention recently for its contribution to protein trafficking, localization, and interaction in various synaptic plasticity. The membrane-associated guanylate kinase (MAGUK) family includes PSD-95, PSD-93 (also known as chapsyn-110), SAP102, …

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …

Inhibition Of Acid Sphingomyelinase Reduces Reactive Astrocyte Secretion Of Mitotoxic Extracellular Vesicles And Improves Alzheimer’S Disease Pathology In The 5xfad Mouse, Simone M. Crivelli, Zainuddin Quadri, Hemendra J. Vekaria, Zhihui Zhu, Priyanka Tripathi, Ahmed Elsherbini, Liping Zhang, Patrick G. Sullivan, Erhard Bieberich

Markey Cancer Center Faculty Publications

In Alzheimer’s disease (AD), reactive astrocytes produce extracellular vesicles (EVs) that affect mitochondria in neurons. Here, we show that Aβ-induced generation of the sphingolipid ceramide by acid sphingomyelinase (A-SMase) triggered proinflammatory cytokine (C1q, TNF-α, IL-1α) release by microglia, which induced the reactive astrocytes phenotype and secretion of EVs enriched with ceramide. These EVs impeded the capacity of neurons to respond to energy demand. Inhibition of A-SMase with Arc39 and Imipramine reduced the secretion of cytokines from microglia, prompting us to test the effect of Imipramine on EV secretion and AD pathology in the 5xFAD mouse model. Brain derived-EVs from 5xFAD …

Examining The Use Of Expressive Arts Therapies In Neurorehabilitation Treatment Planning, Rebecca J. Horner

Expressive Therapies Capstone Theses

Those undergoing neurorehabilitation after stroke and traumatic brain injury report a diminished sense of overall wellness. This paper examines the conceivable benefits of introducing expressive arts therapies, which is the therapeutic use and combination of the visual arts, movement, drama, music, writing and other intermodal creative processes, into physical therapy and neurorehabilitation treatment planning. Expressive arts therapies have the capacity to engage with an individual’s physical, emotional, social and spiritual states concurrently. They simultaneously offer the ability to promote an increased sense of well-being, address mind-body disconnects, and process trauma non-verbally.

The sections of this narrative literature review focus on …

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …

Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain

Saha Cardiovascular Research Center Faculty Publications

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Alzheimer's Disease, Dylan L. Weber

Student Publications

An overview of the background, etiology, pathophysiology, clinical features, diagnosis, treatment and prevention of Alzheimer's disease.

Brain Functional Topology Differs By Sex In Cognitively Normal Older Adults, Zhengshi Yang, Filippo Cieri, Jefferson W. Kinney, Jeffrey L. Cummings, Dietmar Cordes, Jessica Z K Caldwell

Brain Health Faculty Research

Introduction: Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of …

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

A Preliminary Report: The Hippocampus And Surrounding Temporal Cortex Of Patients With Schizophrenia Have Impaired Blood-Brain Barrier, Eric L. Goldwaser, Randel L. Swanson, Edgardo J. Arroyo, Venkat Venkataraman, Mary C. Kosciuk, Robert G. Nagele, L. Elliot Hong, Nimish K. Acharya

Rowan-Virtua Research Day

Schizophrenia (SZ) is one of the most severe forms of mental illness, yet mechanisms remain unclear. A widely established brain finding in SZ is hippocampal atrophy, and a coherent explanation similarly is lacking. Epidemiological evidence suggests increased cerebrovascular and cardiovascular complications in SZ independent of lifestyle and medication, pointing to disease-specific pathology. Endothelial cell contributions to blood-brain barrier (BBB) compromise may influence neurovascular unit and peripheral vascular function, and we hypothesize that downstream functional and structural abnormalities may be explained by impaired BBB.

The Effects Of Paclitaxel On Cellular Migration And The Cytoskeleton, Ashley Salguero-Gonzalez

Thinking Matters Symposium

In a clinical setting, some patients are exposed to an anti-cancer chemotherapy agent, paclitaxel. Cancerous cells undergo rapid, continuous cell division without control. Chemotherapy treatments try to slow and stop the uncontrollable cell division cycles and eliminate cancerous cells in the process. Paclitaxel serves as a treatment for some types of cancers, including lung, melanoma, bladder, and esophageal. Because it targets the cytoskeleton, paclitaxel can also influence cell migration. This project utilizes a cellular migration assay and an immunohistochemistry assay to analyze the effects of paclitaxel on the movement of cells and on the cytoskeleton of neuroglia rat cells with …

Alzheimer's And Patient Caregiver Burnout: A Review Of The Literature, Madeline Hekeler

James Madison Undergraduate Research Journal (JMURJ)

The term “silent epidemic” is fitting for Alzheimer’s disease (AD), as its negative impact is widely felt but rarely discussed. Burnout among AD caregivers has become an epidemic of its own as caregivers experience an increase in health risks, stress, and financial burden. This literature review focuses on caregiver burnout and how imperative it is that caregivers are better supported in their role. Researchers have developed instruments to assess and intervene in caregiver burnout that have shown effectiveness among caregivers and their families.Nevertheless, further longitudinal research is warranted regarding more effective interventions, including stress management and social support mechanisms.

Prmt5 Interacting Partners And Substrates In Oligodendrocyte Lineage Cells, David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patricia Casaccia

Advanced Science Research Center

The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells …

Seizure Prediction In Epilepsy Patients, Gary Dean Cravens

NSU REACH and IPE Day

Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has shown states corresponding to …

Recent Advances In Our Molecular And Mechanistic Understanding Of Misfolded Cellular Proteins In Alzheimer’S Disease (Ad) And Prion Disease (Prd), Walter J. Lukiw

School of Medicine Faculty Publications

Naturally occurring neuron-abundant proteins including amyloid Aβ42 peptide and the microtubule-associated protein tau (MAPT) can, over time and under pathological situations, assume atypical conformations, altering their normal biological structure and function, and causing them to aggregate into insoluble and neurotoxic intracellular inclusions. These misfolded proteins ultimately contribute to the pathogenesis of several progressive, age-related and ultimately lethal human neurodegenerative disorders. The molecular mechanism of this pathological phenomenon of neuronal protein misfolding lends support to the ‘prion hypothesis’, which predicts that the aberrant folding of endogenous natural protein structures into unusual pathogenic isoforms can induce the atypical folding of other similar …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

New Inroads Into Our Understanding Of The Tauopathies, Alzheimer's Disease, And The Contribution Of Altered Protein Conformation To Human Neurological Disease, Walter J. Lukiw

School of Medicine Faculty Publications

No abstract provided.

Stereotactic Radiosurgery For Pituitary Adenomas: A Review Of Literature, Kaynat Siddiqui, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Mechanisms Of Memory Updating: State Dependency Vs. Reconsolidation, Christopher Kiley, Colleen M. Parks

Psychology Faculty Research

Reactivating a memory trace has been argued to put it in a fragile state where it must undergo a stabilization process known as reconsolidation. During this process, memories are thought to be susceptible to interference and can be updated with new information. In the spatial context paradigm, memory updating has been shown to occur when new information is presented in the same spatial context as old information, an effect attributed to a reconsolidation process. However, the integration concept holds that memory change can only occur when reactivation and test states are the same, similar to a state-dependent effect. Thus, in …

Chronic Long-Covid Syndrome: A Protracted Covid-19 Illness With Neurological Dysfunctions, Abdul Mannan Baig

Department of Biological & Biomedical Sciences

After almost a year of COVID-19, the chronic long-COVID syndrome has been recognized as an entity in 2021. The patients with the long-COVID are presenting with ominous neurological deficits that with time are becoming persistent and are causing disabilities in the affected individuals. The mechanisms underlying the neurological syndrome in long-COVID have remained obscure and need to be actively researched to find a resolution for the patients with long-COVID. Here, the factors like site of viral load, the differential immune response, neurodegenerative changes, and inflammation as possible causative factors are debated to understand and investigate the pathogenesis of neuro-COVID in …

Apathy And Brain Atrophy During The First Year Of Moderate-Severe Traumatic Brain Injury: A Longitudinal Study, Gulnaz Kudoiarova

Dissertations, Theses, and Capstone Projects

Apathy, defined as disinterest and loss of motivation, is a common complication after moderate-severe traumatic brain injury (msTBI). The existing body of research in various neurological and neurodegenerative disorders suggests that apathetic symptoms may be associated with variation in the volume of the brain regions such as dorsal anterior cingulate cortex and ventral striatum. However, the longitudinal pattern of TBI-induced atrophy in these key regions and its relationship with apathy symptoms remain to be demonstrated. The current study aimed to describe the atrophy pattern in the anterior cingulate gyrus (ACG) and the nucleus accumbens (NAc; part of ventral striatum) after …

Dimensionality Reduction For Classification Of Object Weight From Electromyography, Elnaz Lashgari, Uri Maoz

Psychology Faculty Articles and Research

Electromyography (EMG) is a simple, non-invasive, and cost-effective technology for measuring muscle activity. However, multi-muscle EMG is also a noisy, complex, and high-dimensional signal. It has nevertheless been widely used in a host of human-machine-interface applications (electrical wheelchairs, virtual computer mice, prosthesis, robotic fingers, etc.) and, in particular, to measure the reach-and-grasp motions of the human hand. Here, we developed an automated pipeline to predict object weight in a reach-grasp-lift task from an open dataset, relying only on EMG data. In doing so, we shifted the focus from manual feature-engineering to automated feature-extraction by using pre-processed EMG signals and thus …