Neurosciences Commons^™

An Excitatory Projection From The Basal Forebrain To The Ventral Tegmental Area That Underlies Anorexia-Like Phenotypes, Jing Cai, Yanyan Jiang, Yuanzhong Xu, Zhiying Jiang, Claire Young, Hongli Li, Joshua Ortiz-Guzman, Yizhou Zhuo, Yulong Li, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of …

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 …

Parenting Influences On Frontal Lobe Gray Matter And Preterm Toddlers' Problem-Solving Skills, Josselyn S Muñoz, Megan E Giles, Kelly A Vaughn, Ying Wang, Susan H Landry, Johanna R Bick, Dana M Demaster

Faculty, Staff and Student Publications

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15–30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers’ natural sleep. The sample contained three gestational groups: 22–27 weeks (extremely preterm; EPT), 28–33 weeks (very preterm; VPT), and 34–36 weeks (late preterm; LPT). Older toddlers became more compliant as …

Insights Of Clinical Significance From 109 695 Solid Tumor Tissue-Based Comprehensive Genomic Profiles, Andreas M Heilmann, Jonathan W Riess, Margaret Mclaughlin-Drubin, Richard S P Huang, Meghann Hjulstrom, James Creeden, Brian M Alexander, Rachel L Erlich

Faculty, Staff and Student Publications

BACKGROUND: FoundationOneCDx is approved in the US and Japan as a companion diagnostic test to identify patients with cancer who may benefit from treatment with 30 drug therapies in the US and 23 in Japan. Tumor profiling with FoundationOneCDx also detects genomic findings with evidence of clinical significance that may inform clinical care decisions beyond companion diagnostic claims. This observational study reports the breadth and impact of clinical decision insights from FoundationOneCDx solid tumor profiles.

MATERIALS AND METHODS: Consecutive test result reports for patients with solid tumor diagnoses (n = 109 695) were retrospectively analyzed for clinically significant predictive, prognostic, …

Sarin-Induced Neuroinflammation In Mouse Brain Is Attenuated By The Caspase Inhibitor Q-Vd-Oph, Ekta J. Shah, William C. Grunwald Jr., Teresa L. Garrett, Thomas L. Brown, David R. Cool

Neuroscience, Cell Biology & Physiology Faculty Publications

Organophosphates cause hyperstimulation of the central nervous system, leading to extended seizures, convulsions, and brain damage. Sarin is a highly toxic organophosphate nerve agent that has been employed in several terrorist attacks. The prolonged toxicity of sarin may be enhanced by the neuroinflammatory response initiated by the inflammasome, caspase involvement, and generation/release of proinflammatory cytokines. Since neurodegeneration and neuroinflammation are prevalent in sarin-exposed animals, we were interested in evaluating the capacity of quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone (Q-VD-OPh), a pan caspase inhibitor to attenuate neuroinflammation following sarin exposure. To test this hypothesis, sarin-exposed C57BL/6 mice were treated with Q-VD-OPh or negative control quinolyl-valyl-O-methylglutamyl-[-2,6-difluorophenoxy]-methyl …

Neurologic Morbidity And Functional Independence In Adult Survivors Of Childhood Cancer, Stefanie C Vuotto, Mingjuan Wang, M Fatih Okcu, Daniel C Bowers, Nicole J Ullrich, Kirsten K Ness, Chenghong Li, Deo Kumar Srivastava, Rebecca M Howell, Todd M Gibson, Wendy M Leisenring, Kevin C Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull, Tara M Brinkman

Faculty, Staff and Student Publications

OBJECTIVE: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)-directed therapies.

METHODS: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS-treated]; median age [range] = 25.5 years [18-48]; time since diagnosis = 17.7 years [6.8-30.2]) and 8039 without CNS-directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal …

Cognitive Reserve In Individuals With Frontotemporal Dementia And Primary Progressive Aphasia, Lauren A. Grebe

Dissertations, Theses, and Capstone Projects

Cognitive reserve refers to the brain’s ability to efficiently adapt in the presence of neuropathological disease. This is an active process influenced by individual differences (e.g., genetics) and lifetime experiences (e.g., education, occupation, leisure) (Cabeza et al., 2018; Stern et al., 2020). The cognitive reserve theory has recently been investigated in individuals with frontotemporal dementia (FTD), which refers to various disorders leading to frontotemporal neurodegenerative decline (Young et al., 2018); e.g., behavioral variant of FTD (bvFTD) and variants of Primary Progressive Aphasia (PPA): semantic (svPPA), nonfluent/agrammatic (nfvPPA), and logopenic (lvPPA). However, a clear consensus on the relationship among cognitive reserve, …

Submental Island Flaps For Lateral Reconstruction: Technical Refinements For Optimal Outcomes And Resource Efficiency, My V H Nguyen, Yinan Xu, Kelly A Vaughn, Arturo E Hernandez

Faculty, Staff and Student Publications

Research suggests that bilingual children experience an extension or delay in the closing of the sensitive/critical period of language development due to multiple language exposure. Moreover, bilingual experience may impact the development of subcortical regions, although these conclusions are drawn from research with adults, as there is a scarcity of research during late childhood and early adolescence. The current study included 1215 bilingual and 5894 monolingual children from the ABCD Study to examine the relationship between subcortical volume and English vocabulary in heritage Spanish bilingual and English monolingual children, as well as volumetric differences between the language groups. We also …

Large-Scale Investigation Of White Matter Structural Differences In Bilingual And Monolingual Children: An Adolescent Brain Cognitive Development Data Study, Juliana Ronderos, Jennifer Zuk, Arturo E Hernandez, Kelly A Vaughn

Faculty, Staff and Student Publications

Emerging research has provided valuable insights into the structural characteristics of the bilingual brain from studies of bilingual adults; however, there is a dearth of evidence examining brain structural alterations in childhood associated with the bilingual experience. This study examined the associations between bilingualism and white matter organization in bilingual children compared to monolingual peers leveraging the large-scale data from the Adolescent Brain Cognitive Development (ABCD) Study. Then, 446 bilingual children (ages 9-10) were identified from the participants in the ABCD data and rigorously matched to a group of 446 monolingual peers. Multiple regression models for selected language and cognitive …

Activation Of Testosterone-Androgen Receptor Mediates Cerebrovascular Protection By Photobiomodulation Treatment In Photothrombosis-Induced Stroke Rats, Yu Feng, Zhihai Huang, Xiaohui Ma, Xuemei Zong, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin, Michael R Hamblin, Quanguang Zhang

Faculty, Staff and Student Publications

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown.

METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with …

Tumor Treating Fields Increases Blood-Brain Barrier Permeability And Relative Cerebral Blood Volume In Patients With Glioblastoma, Michael Iv, Lewis Naya, Sajal Sanan, Samuel L Van Buskirk, Seema Nagpal, Reena P Thomas, Lawrence D Recht, Chirag B Patel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: 200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.

METHODS: Each patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (V

RESULTS: Among 13 pMRI datasets …

Publisher Correction: Long-Term Labeling And Imaging Of Synaptically Connected Neuronal Networks In Vivo Using Double-Deletion-Mutant Rabies Viruses, Lei Jin, Heather A Sullivan, Mulangma Zhu, Thomas K Lavin, Makoto Matsuyama, Xin Fu, Nicholas E Lea, Ran Xu, Yuanyuan Hou, Luca Rutigliani, Maxwell Pruner, Kelsey R Babcock, Jacque Pak Kan Ip, Ming Hu, Tanya L Daigle, Hongkui Zeng, Mriganka Sur, Guoping Feng, Ian R Wickersham

Faculty, Staff and Students Publications

This corrects the article "Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses" on page 373.

Long-Term Labeling And Imaging Of Synaptically Connected Neuronal Networks In Vivo Using Double-Deletion-Mutant Rabies Viruses, Lei Jin, Heather A Sullivan, Mulangma Zhu, Thomas K Lavin, Makoto Matsuyama, Xin Fu, Nicholas E Lea, Ran Xu, Yuanyuan Hou, Luca Rutigliani, Maxwell Pruner, Kelsey R Babcock, Jacque Pak Kan Ip, Ming Hu, Tanya L Daigle, Hongkui Zeng, Mriganka Sur, Guoping Feng, Ian R Wickersham

Faculty, Staff and Students Publications

Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans in postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Generation Of A Dcx-Creert2 Knock-In Mouse For Genetic Manipulation Of Newborn Neurons, Gabriella A Perez, Kyung-Won Park, Denise Lanza, Jenna Cicardo, M Danish Uddin, Joanna L Jankowsky

Faculty, Staff and Students Publications

A wide variety of CreERT2 driver lines are available for genetic manipulation of adult-born neurons in the mouse brain. These tools have been instrumental in studying fate potential, migration, circuit integration, and morphology of the stem cells supporting lifelong neurogenesis. Despite a wealth of tools, genetic manipulation of adult-born neurons for circuit and behavioral studies has been limited by poor specificity of many driver lines targeting early progenitor cells and by the inaccessibility of lines selective for later stages of neuronal maturation. We sought to address these limitations by creating a new CreERT2 driver line targeted to the endogenous mouse …

Generation Of Five Induced Pluripotent Stem Cell Lines From Patients With Mecp2 Duplication Syndrome, Danielle Mendonca, Gerarda Cappuccio, Jennifer Sheppard, Magdalena Delacruz, Jesse Bengtsson, Claudia M B Carvalho, Aleksandar Bajic, Hyekyung Park, Jean J Kim, Paymaan Jafar-Nejad, Christine Coquery, Davut Pehlivan, Bernhard Suter, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.

Using Mobile Technology For Family-Based Prevention In Families With Low Incomes: Lessons From A Randomized Controlled Trial Of A Childhood Obesity Prevention Program, Thomas G Power, Susan S Baker, Karen V Barale, M Catalina Aragón, Jane D Lanigan, Louise Parker, Karina Silva Garcia, Garry Auld, Nilda Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Researchers are increasingly using web-based technologies to deliver family-based, prevention programming. Few studies have examined the success of such approaches for families with low incomes. The purpose of this study was to describe the level of in-class and online engagement in a childhood obesity prevention program for parents with low incomes, to examine the demographic correlates of parent engagement, and to examine dosage effects on parental feeding outcomes as a function of online exposure. All participants attended in-class nutrition education classes (Eating Smart · Being Active) as part of the Expanded Food and Nutrition Education Program (EFNEP) in Colorado and …

Novel Hemizygous Single-Nucleotide Duplication In Rpgr In A Patient With Retinal Dystrophy And Sensorineural Hearing Loss, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Nichole Owen, Richard A Lewis, Lisa Saba, Texome Project, Michael F Wangler, Sandesh Nagamani

Duncan NRI Faculty and Staff Publications

Background: The RPGR gene has been associated with X-linked cone-rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel-based testing and thus genome-wide tests such as ES may be required for accurate diagnosis.

Methods: The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care.

Results: A 58-year-old male presented with retinitis pigmentosa, sensorineural hearing loss, and …

Matr3 Pathogenic Variants Differentially Impair Its Cryptic Splicing Repression Function, Mashiat Khan, Xiao Xiao Lily Chen, Michelle Dias, Jhune Rizsan Santos, Sukhleen Kour, Justin You, Rebekah Van Bruggen, Mohieldin M M Youssef, Ying-Wooi Wan, Zhandong Liu, Jill A Rosenfeld, Qiumin Tan, Udai Bhan Pandey, Hari Krishna Yalamanchili, Jeehye Park

Duncan NRI Faculty and Staff Publications

Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated variants impact this function. We show that loss of MATR3 leads to cryptic exon inclusion in many transcripts. We reveal that ALS-linked S85C pathogenic variant reduces MATR3 solubility but does not impair RNA binding. In parallel, we report a novel neurodevelopmental disease-associated M548T variant, located in the RRM2 domain, which reduces protein solubility and impairs RNA binding and cryptic splicing repression functions of MATR3. Altogether, our research …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

The Importance Of Considering Competing Risks In Recurrence Analysis Of Intracranial Meningioma, Christian Mirian, Lasse Rehné Jensen, Tareq A Juratli, Andrea Daniela Maier, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Fuyou Guo, Pedro Góes, Manoel Antonio De Paiva Neto, Aria Jamshidi, Ricardo Komotar, Michael Ivan, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Anders Broechner, Mathias Jacobsen Bach, Ian Law, David Scheie, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated.

METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage …

Number Of Children In The Household Influences Respiratory Morbidities In Children With Bronchopulmonary Dysplasia In The Outpatient Setting, Joseph M Collaco, Katharine R Tsukahara, Michael C Tracy, Catherine A Sheils, Jessica L Rice, Lawrence M Rhein, Antonia P Popova, Leif Nelin, Audrey N Miller, Winston M Manimtim, Jonathan C Levin, Khanh Lai, Jacob A Kaslow, Lystra P Hayden, Manvi Bansal, Eric D Austin, Brianna Aoyama, Gangaram Akangire, Amit Agarwal, Natalie Villafranco, Sharon A Mcgrath-Morrow

Faculty, Staff and Students Publications

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with outpatient morbidities, including respiratory exacerbations. Daycare attendance is associated with increased rates of acute and chronic morbidities in children with BPD. We sought to determine if additional children in the household conferred similar risks for children with BPD.

METHODS: The number of children in the household and clinical outcomes were obtained via validated instruments for 933 subjects recruited from 13 BPD specialty clinics in the United States. Clustered logistic regression models were used to test for associations.

RESULTS: The mean gestational age of the study population was 26.5 …

The Role Of Diet And Gut Microbiota In Alzheimer’S Disease, D. M.Sithara Dissanayaka, Vijay Jayasena, Stephanie R. Rainey-Smith, Ralph N. Martins, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by the accumulation of amyloid-beta (A ) plaques and hyperphosphorylated tau tangles. Currently, Alzheimer’s disease (AD) impacts 50 million individuals, with projections anticipating an increase to 152 million by the year 2050. Despite the increasing global prevalence of AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis and treatment. Recent research suggests a link between gut dysbiosis and the aggregation of A , the development of tau proteins, and the occurrence of neuroinflammation and oxidative stress are associated with AD. However, investigations into the gut–brain axis …

Investigating The Association Between Gut Bacteria And Childhood Neuropsychiatric Disorders, Maha Abdo

Theses and Dissertations

Background: The etiology of autism spectrum disorder (ASD) remains unclear. However, it’s believed to be a multifactorial condition. Several studies suggest the involvement of gut and oral microbiome in the predisposition of ASD symptoms. Understanding the pathophysiology could aid in developing better treatment strategies that improve the quality of life of ASD individuals and their caregivers.

Aim: The current study aims at characterizing the gut and oral microbiome composition of ASD children compared to their healthy siblings and mothers as control groups.

Methods: Stool and saliva samples were collected from fourteen families at Ain Shams University Hospital, Outpatient Clinic. The …

Brain-Derived Neurotrophic Factor (Bdnf) Signaling Mechanisms That Regulate Learning And Memory In Rats, Clementine Faye Harvey

Theses - ALL

Brain-derived neurotrophic factor (BDNF) is a widespread neurotrophin implicated in cellular processes underlying memory, socialization, and emotion; however, little is known about how genetic modification of BDNF interacts with BDNF modulators (e.g., hormones) to regulate BDNF-TrkB signaling. BDNF binds to the TrkB receptor and triggers signaling cascades underlying neuroplasticity, learning, and memory. Inhibitory phosphorylation of one downstream target of the BDNF cascade - GSK3β – is also linked to memory improvements. The Val66Met allele – a single nucleotide polymorphism (SNP) in the Bdnf gene - produces impairments in regulated BDNF release from the cell, as well as deficits in spatial …

Sex-Specific Negative Affect-Like Behaviour And Parabrachial Nucleus Activation Induced By Bnst Stimulation In Adult Mice With Adolescent Alcohol History, Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills

School of Medicine Faculty Publications

Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute …

Role Of Polyunsaturated Fat In Modifying Cardiovascular Risk Associated With Family History Of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies, Federica Laguzzi, Agneta Åkesson, Matti Marklund, Frank Qian, Bruna Gigante, Traci M Bartz, Julie K Bassett, Anna Birukov, Hannia Campos, Yoichiro Hirakawa, Fumiaki Imamura, Susanne Jäger, Maria Lankinen, Rachel A Murphy, Mackenzie Senn, Toshiko Tanaka, Nathan Tintle, Jyrki K Virtanen, Kazumasa Yamagishi, Matthew Allison, Ingeborg A Brouwer, Ulf De Faire, Gudny Eiriksdottir, Luigi Ferrucci, Nita G Forouhi, Johanna M Geleijnse, Allison M Hodge, Hitomi Kimura, Markku Laakso, Ulf Risérus, Anniek C Van Westing, Stefania Bandinelli, Ana Baylin, Graham G Giles, Vilmundur Gudnason, Hiroyasu Iso, Rozenn N Lemaitre, Toshiharu Ninomiya, Wendy S Post, Bruce M Psaty, Jukka T Salonen, Matthias B Schulze, Michael Y Tsai, Matti Uusitupa, Nicholas J Wareham, Seung-Won Oh, Alexis C Wood, William S Harris, David Siscovick, Dariush Mozaffarian, Karin Leander, Fatty Acids And Outcomes Research Consortium (Force)

Faculty, Staff and Students Publications

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium.

METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were …

Revitalizing Alzheimer's Community Engagement In The Rgv Post-Pandemic: Insights From The First Two Alzheimer's Forums, Karla D. Lopez Lorenzo, Maxine Vieyra, Jesus D. Melgarejo, Gladys E. Maestre

Research Symposium

Background: The Rio Grande Valley (RGV), with a population predominantly composed of Hispanic/Latinos (93%), faces a higher risk of Alzheimer's Disease (AD) compared to other groups. The COVID-19 pandemic has highlighted the lack of education and awareness surrounding AD and related dementias in our community. To address these challenges, we partnered with the Alzheimer's Association to organize the first two Community Forums after the pandemic. Our goal is to raise awareness, provide resources, and support those affected by AD and related conditions in the RGV.

Methods: Through a proactive partnership, our objective was to meet the growing demand for education, …

Chronic Cannabis Use Is Associated With Decreased Treatment Response In Major Depression, Ihsan Salloum

Research Symposium

Background: Cannabis is the most frequently used federally illegal drug among the population and those receiving psychiatric treatment, including patients with major depression or alcohol use disorder. There is limited information on the impact of chronic cannabis use on treatment response. The aim of this study was to examine the rate of depression remission among patients with MDD and comorbid alcoholism who reported chronic cannabis abuse.

Methods: Sixty-four subjects with comorbid major depressive disorder and alcohol dependence (PRISM/DSM-IV), and a chronic (=>10 years) history of cannabis use (n=26) were compared to those who reported occasional or no cannabis …

Deepvelo: Deep Learning Extends Rna Velocity To Multi-Lineage Systems With Cell-Specific Kinetics, Haotian Cui, Hassaan Maan, Maria C Vladoiu, Jiao Zhang, Michael D Taylor, Bo Wang

Faculty, Staff and Students Publications

Existing RNA velocity estimation methods strongly rely on predefined dynamics and cell-agnostic constant transcriptional kinetic rates, assumptions often violated in complex and heterogeneous single-cell RNA sequencing (scRNA-seq) data. Using a graph convolution network, DeepVelo overcomes these limitations by generalizing RNA velocity to cell populations containing time-dependent kinetics and multiple lineages. DeepVelo infers time-varying cellular rates of transcription, splicing, and degradation, recovers each cell's stage in the differentiation process, and detects functionally relevant driver genes regulating these processes. Application to various developmental and pathogenic processes demonstrates DeepVelo's capacity to study complex differentiation and lineage decision events in heterogeneous scRNA-seq data.