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2024

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Full-Text Articles in Molecular and Cellular Neuroscience

Regulation And Function Of Mec-2 Alternative Splicing In Single Cells, Canyon Calovich-Benne Dec 2024

Regulation And Function Of Mec-2 Alternative Splicing In Single Cells, Canyon Calovich-Benne

Biological Sciences Theses and Dissertations

One mechanism for generating diversity at the single cell level is selective expression of a unique set of transcription factors (TFs) and RNA binding proteins (RBPs). These regulatory factors contribute to functions of cells by controlling cell fate, turning genes on and off, and processing of transcripts either co- or post-transcriptionally. Many genes, especially neuronal genes, have multiple different splicing events, promoters, and/or polyadenylation sites. Post-transcriptional coordination is in the infancy of being studied and the functional consequences of this coupling at the single cell level has yet to be explored. Here we show, mec-2 coordination of alternative transcription start …


Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia Dec 2024

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …


Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk Dec 2024

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …


Medial Prefrontal Cortex To Nucleus Reuniens Circuit Is Critical For Performance In An Operant Delayed Nonmatch To Position Task, Evan J Ciacciarelli, Scott D Dunn, Taqdees Gohar, T Joseph Sloand, Mark Niedringhaus, Elizabeth A West Nov 2024

Medial Prefrontal Cortex To Nucleus Reuniens Circuit Is Critical For Performance In An Operant Delayed Nonmatch To Position Task, Evan J Ciacciarelli, Scott D Dunn, Taqdees Gohar, T Joseph Sloand, Mark Niedringhaus, Elizabeth A West

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Working memory refers to the temporary retention of a small amount of information used in the execution of a cognitive task. The prefrontal cortex and its connections with thalamic subregions are thought to mediate specific aspects of working memory, including engaging with the hippocampus to mediate memory retrieval. We used an operant delayed-non match to position task, which does not require the hippocampus, to determine roles of the rodent medial prefrontal cortex (mPFC), the nucleus reuniens thalamic region (RE), and their connection. We found that transient inactivation of the mPFC and RE using the GABA-A agonist muscimol led to a …


Increased Neuroinflammation And Compromised Blood Brain Barrier In A Mouse Model Of Autism, Amani S. Ikram, Rekha Jagadapillai, Idil Tuncali, Gregory N. Barnes, Evelyne Gozal Nov 2024

Increased Neuroinflammation And Compromised Blood Brain Barrier In A Mouse Model Of Autism, Amani S. Ikram, Rekha Jagadapillai, Idil Tuncali, Gregory N. Barnes, Evelyne Gozal

The Cardinal Edge

No abstract provided.


Use Of Electrical Bone Growth Stimulators In High-Risk Patients Following Spinal Fusion, Soumya Malhotra, Khavir Sharieff Nov 2024

Use Of Electrical Bone Growth Stimulators In High-Risk Patients Following Spinal Fusion, Soumya Malhotra, Khavir Sharieff

HCA-NSU MD Research Day

Title: Use of Electrical Bone Growth Stimulators in High-Risk Patients Following Spinal Fusion Authors: Soumya Malhotra, BA., MS1 & Khavir Sharieff, DO, MBA2 1Class of 2027, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Fort Lauderdale, FL 2Assistant Professor of Surgery, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Tampa Bay, FLNova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine Objective: This study aimed to elucidate the advantages of EBGSs following high-risk spinal fusions. Background: Pseudarthrosis is a condition where bones fail to fuse after an injury or surgery. It causes significant …


Effects Of Retinal Gonadotropin-Releasing Hormone On Reproductive Behavior And Retinal Activity In The Cichlid Fish, Astatotilapia Burtoni, Chase Anselmo Oct 2024

Effects Of Retinal Gonadotropin-Releasing Hormone On Reproductive Behavior And Retinal Activity In The Cichlid Fish, Astatotilapia Burtoni, Chase Anselmo

LSU Master's Theses

Many animals use visual signals to evade predators, forage for food, and communicate with conspecifics. Some animals that shift into and out of breeding stages, such as fish, can modulate their visual sensitivity to better adapt to changing internal and external conditions. Previous work in our lab demonstrated that females of the cichlid fish Astatotilapia burtoni have improved visual sensitivity when they enter reproductive readiness. However, little is known about how fish and vertebrates more broadly modulate visual sensitivity across their reproductive cycle. We hypothesized that the hormone and neuromodulator gonadotropin-releasing hormone (GnRH) could modulate visual sensitivity because GnRH is …


Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós Oct 2024

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …


Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee Oct 2024

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …


Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean Sep 2024

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …


Sex-Dependent Gene Expression Alterations In Social Defeat Stress Model Of Major Depression Disorder, Juan Diego Torres, Javier Vargas Medrano, Anapaula Themann, Elias Arellano Villanueva, Nina Mourao, Megan W. Szobody, Tori Sayers, Sriya Gullapalli, Tyler Torres, Sridhar Srinivasan, Anesu Karen Murambadoro, Kory Deshawn Punch, Kevin Valdez Garcia, Nikhilesh Anand, Kelsey Baker, Sergio Iniguez, Bharathi Shrikanth Gadad Sep 2024

Sex-Dependent Gene Expression Alterations In Social Defeat Stress Model Of Major Depression Disorder, Juan Diego Torres, Javier Vargas Medrano, Anapaula Themann, Elias Arellano Villanueva, Nina Mourao, Megan W. Szobody, Tori Sayers, Sriya Gullapalli, Tyler Torres, Sridhar Srinivasan, Anesu Karen Murambadoro, Kory Deshawn Punch, Kevin Valdez Garcia, Nikhilesh Anand, Kelsey Baker, Sergio Iniguez, Bharathi Shrikanth Gadad

Research Colloquium

Introduction: Major Depression Disorder (MDD) is a prevalent, recurrent, and chronic disorder that represents a leading cause of disability worldwide. Millions are affected with symptoms that go from constant sadness to even suicidal thoughts. In the U.S., major depression and fatal suicide have increased by 57.4% among adolescents and young adults. Myelin and inflammation-related genes have been found to play a role in individuals with MDD.

Methods: Adolescent males and females C57BL/6 mice underwent a vicarious defeat stress (VDS) procedure in which a mouse witnessed a conspecific being defeated. VDS and control (CON) mice underwent the Social Interaction (SI) test. …


Molecular Studies In Understanding Novel Curcumin-Glucoside Role In The Prevention Of Alpha-Synuclein Aggregation In Relevance To Parkinson's Disease, Natasha N. Quailes, Nina Mourao, Megan W. Szobody, Sridhar Srinivasan, Sriya Gullapalli, Elias Arellano Villanueva, Tyler Torres, Kory Deshawn Punch, Anesu Karen Murambadoro, Blake Martin, Kelsey Baker, Nikhilesh Anand, Hansapani Rodrigo, Bharathi Shrikanth Gadad Sep 2024

Molecular Studies In Understanding Novel Curcumin-Glucoside Role In The Prevention Of Alpha-Synuclein Aggregation In Relevance To Parkinson's Disease, Natasha N. Quailes, Nina Mourao, Megan W. Szobody, Sridhar Srinivasan, Sriya Gullapalli, Elias Arellano Villanueva, Tyler Torres, Kory Deshawn Punch, Anesu Karen Murambadoro, Blake Martin, Kelsey Baker, Nikhilesh Anand, Hansapani Rodrigo, Bharathi Shrikanth Gadad

Research Colloquium

Background: The synuclein deposition in the brain of Parkinson’s Disease (PD) is the hallmark pathology of the neurodegenerative pathway. The transformation of alpha-synuclein into synuclein monomer, toxic oligomer, and insoluble fibrils are key steps in cell dysfunction. We synthesized a novel molecule, Curcumin-glucoside (Curc-gluc), which has good water solubility and a favorable partition coefficient.

Methods: The present study focuses on α-syn aggregation kinetics in the presence and absence of Curc-gluc and Curcumin; we also tested the effect of Copper (Cu) and Iron (Fe) Fe binding through a mathematical approach, biophysical techniques, and docking models. In the mathematical approach, we applied …


Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled Sep 2024

Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled

Undergraduate Research Symposium

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction …


Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma Sep 2024

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …


Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum Sep 2024

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …


Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra Sep 2024

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …


The Role Of The Circadian Clock In The Paraventricular Nucleus Of The Hypothalamus In Diurnal Energy Balance, Rachel Van Drunen Aug 2024

The Role Of The Circadian Clock In The Paraventricular Nucleus Of The Hypothalamus In Diurnal Energy Balance, Rachel Van Drunen

Dissertations and Theses (Open Access)

Circadian rhythms are internal biological rhythms that drive oscillations in physiology and metabolism. Maintained at the level of individual cells throughout the body, the circadian clock is necessary for driving tissue-specific temporal programs of energy balance. Though loss of the circadian transcription factor, BMAL1, in the paraventricular nucleus (PVN) of the hypothalamus has revealed its importance in driving rhythms in energy intake and metabolism, its transcriptional functions across time and in individual cell types in the PVN are not well understood. In this study, we show that loss of BMAL1 in the PVN not only results in arrhythmicity in processes …


Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu Aug 2024

Cerebrovascular Reactivity Mri As A Biomarker For Cerebral Small Vessel Disease–Related Cognitive Decline: Multi-Site Validation In The Markvcid Consortium, Peiying Liu, Zixuan Lin, Kaisha Hazel, George Pottanat, Cuimei Xu, Dengrong Jiang, Jay J. Pillai, Emma Lucke, Christopher E. Bauer, Brian T. Gold, Steven M. Greenburg, Karl G. Helmer, Kay Jann, Gregory Jicha, Joel Kramer, Pauline Maillard, Rachel M. Mulavelil, Pavel Rodriguez, Claudia L. Satizabal, Kristin Schwab, Sudha Seshadri, Herpreet Singh, Ángel G. Velarde Dediós, Danny J. J. Wang, Rita R. Kalyani, Abhay Moghekar, Paul B. Rosenberg, Sevil Yasar, Marilyn Albert, Hanzhang Lu

Neurology Faculty Publications

INTRODUCTION: Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

METHODS: We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.

RESULTS: CVR …


Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy Aug 2024

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …


Poly (Adp-Ribose) Polymerase-1 (Parp1) Expression In The Frontal Cortex And Hippocampus In Major Depressive Disorder (Mdd) And Suicide, Ramona Faith Fulkerson Aug 2024

Poly (Adp-Ribose) Polymerase-1 (Parp1) Expression In The Frontal Cortex And Hippocampus In Major Depressive Disorder (Mdd) And Suicide, Ramona Faith Fulkerson

Electronic Theses and Dissertations

Major Depressive Disorder (MDD) is a prevalent psychiatric disorder that has a complex pathophysiology. In this study we evaluate the expression of PARP1 and the downstream alarmin protein high mobility group box 1 (HMGB1) in two brain areas that have demonstrated pathology in MDD. MDD donors were compared to controls. MDD subgroups that died by suicide were also compared to those that did not die by suicide. Immunoblotting to determine PARP1 and HMGB1 protein expression was performed in white and grey matter from the frontal cortex and the hippocampus. In BA10 white and grey matter, PARP1 protein expression was significantly …


Host-Microbiome Interactions In The Teleost Brain, Amir Mani Varnoosfaderani Jul 2024

Host-Microbiome Interactions In The Teleost Brain, Amir Mani Varnoosfaderani

Biology ETDs

This dissertation investigates host-microbial interactions within the teleost brain, previously considered sterile. Reviewing current literature highlights significant gaps in understanding teleost brain immunity, despite prevalent neurotropic diseases. We mapped the immune profiles of rainbow trout brains and meninges, revealing the olfactory bulbs as the immune effector part of the brain and the optic tectum as a nod2 expression hub. High il6 and il10 levels were noted in the telencephalon. A persistent bacterial community within healthy salmonid brains shares diversity with gut and blood microbiota. Brain bacterial isolates exhibit genomic signatures for brain colonization and polyamine biosynthesis. The microbiota shifts across …


Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters Jul 2024

Decentralized Clinical Trials For Medications To Reduce The Risk Of Dementia: Consensus Report And Guidance, Leanne Howard, Carla Abdelnour, Erin Abner, Ricardo F. Allegri, Hiroko H. Dodge, Serge Gauthier, Camilla M. Hoyos, Gregory Jicha, Patrick G. Kehoe, Catherine J. Mummery, Adesola Ogunniyi, Nikolaos Scarmeas, Xiaoying Chen, Jodie R. Titiner, Christopher R. Weber, Ruth Peters

Neurology Faculty Publications

INTRODUCTION: Recent growth in the functionality and use of technology has prompted an increased interest in the potential for remote or decentralized clinical trials in dementia. There are many potential benefits associated with decentralized medication trials, but we currently lack specific recommendations for their delivery in the dementia field.

METHODS: A modified Delphi method engaged an expert panel to develop recommendations for the conduct of decentralized medication trials in dementia prevention. A working group of researchers and clinicians with expertise in dementia trials further refined the recommendations.

RESULTS: Overall, the recommendations support the delivery of decentralized trials in dementia prevention …


A Pathologic Study Of Perivascular Ptdp-43 Lin Bodies In Late-Nc, Ryan K. Shahidehpour, Peter T. Nelson, Adam D. Bachstetter Jul 2024

A Pathologic Study Of Perivascular Ptdp-43 Lin Bodies In Late-Nc, Ryan K. Shahidehpour, Peter T. Nelson, Adam D. Bachstetter

Neurology Faculty Publications

Background TAR DNA-Binding Protein 43 (TDP-43) pathological inclusions are a distinctive feature in dozens of neurodegenerative pathologies, including limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Prior investigations identified vascular-associated TDP-43-positive micro-lesions, known as “Lin bodies,” located on or near the brain capillaries of some individuals with LATE-NC. This study aimed to investigate the relationship between the accumulation of Lin bodies and glial cells in LATE-NC and the potential co-localization with ferritin, a protein associated with iron storage. Using multiplexed immunohistochemistry and digital pathology tools, we conducted pathological analyses to investigate the relationship between Lin bodies and glial markers (GFAP for …


Local And Distal Projections Of Vta Gaba Neurons, Trinity M. Pirrone Jun 2024

Local And Distal Projections Of Vta Gaba Neurons, Trinity M. Pirrone

Neuroscience Honors Projects

Substance use disorder (SUD) is a psychiatric disorder characterized by the abuse of drugs, compulsive drug seeking, and addiction. Addiction is facilitated by social, environmental, genetic, and neurobiological mechanisms. The underlying neural circuitry of addiction encompasses several brain regions, circuits, and cell types contributing to the reward system both collectively and independently. Evidence has shown that the ventral tegmental area of the brain is a control center of reward, an important mechanism for drug-seeking in addiction. Previous research has described the ventral tegmental area as a highly heterogeneous region containing various cell types serving different roles. GABAergic neurons of the …


Complement Propagates Visual System Pathology After Traumatic Brain Injury, Davis Marchant Borucki Jun 2024

Complement Propagates Visual System Pathology After Traumatic Brain Injury, Davis Marchant Borucki

MUSC Theses and Dissertations

Background: Traumatic brain injury is associated with the development of visual system disorders, including deficits in visual acuity. Visual deficits can present with delay and worsen over time, suggesting that ongoing neuroinflammatory changes contribute to their development and progression. Complement activation is strongly associated with the neuroinflammatory response after TBI and has been shown to contribute to neuronal and synaptic loss. However, the contributions of complement activation after TBI to vision loss remains unclear.

Methods: We employed an open skull controlled cortical impact model of traumatic brain injury in adult male mice to study how TBI affects vision. Animals were …


Neural Mechanisms Of Respiratory Interoception, Pei-Ying Sarah Chan, Lu-Yuan Lee, Paul W. Davenport Jun 2024

Neural Mechanisms Of Respiratory Interoception, Pei-Ying Sarah Chan, Lu-Yuan Lee, Paul W. Davenport

UK CARES Faculty Publications

Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. …


Comprehensive Assessment Of Tdp‑43 Neuropathology Data In The National Alzheimer’S Coordinating Center Database, Davis C. Woodworth, Katelynn M. Nguyen, Lorena Sordo, Kiana A. Scambray, Elizabeth Head, Claudia H. Kawas, María M. Corrada, Peter T. Nelson, S. Ahmad Sajjadi Jun 2024

Comprehensive Assessment Of Tdp‑43 Neuropathology Data In The National Alzheimer’S Coordinating Center Database, Davis C. Woodworth, Katelynn M. Nguyen, Lorena Sordo, Kiana A. Scambray, Elizabeth Head, Claudia H. Kawas, María M. Corrada, Peter T. Nelson, S. Ahmad Sajjadi

Neurology Faculty Publications

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer’s Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by …


The Role Of Micrornas On Systemic And Central Nervous System- Inflammation In Aged Mice, Anik Banerjee Jun 2024

The Role Of Micrornas On Systemic And Central Nervous System- Inflammation In Aged Mice, Anik Banerjee

Dissertations and Theses (Open Access)

MicroRNAs play a crucial role in multiple biological processes, including development, cell differentiation, proliferation, metabolism, and cell death. Aberrant regulation of microRNAs is seen in many diseases, such as sepsis, cardiovascular disease, neurological diseases such as stroke, and metabolic disorders. Because of their involvement in disease processes, microRNAs have been investigated as both potential biomarkers, and as therapeutic targets. Age-related inflammatory diseases including diabetes, obesity, and atherosclerosis are important risk factors for infection and sepsis. Intestinal barrier impairment occurs with aging and after brain injuries, including stroke. Both aging and stroke increase the risk of infection and sepsis and are …


Prenatal Alcohol Exposure Induces Anatomical Changes In The Mouse Somatosensory Cortex., Zahra Saad Siddiqui May 2024

Prenatal Alcohol Exposure Induces Anatomical Changes In The Mouse Somatosensory Cortex., Zahra Saad Siddiqui

Dartmouth College Master’s Theses

Atypical tactile responses are implicated in Fetal Alcohol Spectrum Disorders (FASD). Our lab reported diminished tactile sensitivity in young adolescent mice with a history of prenatal alcohol exposure (PAE). Here, I employed immunohistochemistry to investigate the anatomical correlates of altered tactile sensitivity observed in mice with PAE. Using our 3-day binge paradigm, I examined changes in the distribution pattern of pre- (thalamocortical afferents) and postsynaptic (pyramidal neurons) partners involved in processing tactile information in the SSC of Postnatal day (P) 7 mice. In rodents, tactile information is relayed somatotopically to the SSC via TC afferents expressing vesicular glutamate transporter 2 …


Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander May 2024

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H2O2 (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …