Neurosciences Commons^™

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations and Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

Abnormality Of Early White Matter Development In Tuberous Sclerosis Complex And Autism Spectrum Disorder: Longitudinal Analysis Of Diffusion Tensor Imaging Measures, Siddharth Srivastava, Fanghan Yang, Anna K Prohl, Peter E Davis, Jamie K Capal, Rajna Filip-Dhima, E Martina Bebin, Darcy A Krueger, Hope Northrup, Joyce Y Wu, Simon K Warfield, Mustafa Sahin, Bo Zhang, Tacern Study Group

Faculty, Staff and Student Publications

Background:

Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule–Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data.

Methods:

Eligible participants (3-12 months) …

Single Case Experimental Design Examining Cognitive Behavioural Therapy For Post-Stroke Depression, Liam Alexander Mackenzie Myles, Emma Jones

Journal of Mind and Medical Sciences

Background. Post-stroke depression (PSD) is common in older-age adults and is typically treated with cognitive-behavioural therapy (CBT). However, research has ascertained mixed findings regarding the efficacy of CBT for PSD in older-age adults, with limited evidence in people from global majority backgrounds. Materials and Methods. This case study used single case experimental design methodology to examine the effectiveness of CBT for PSD in a black, older-age man. The effects of health conditions, cohort beliefs, transitions in role investments, socio-cultural context and early experiences on the client’s thoughts, emotions, physical sensations and behaviours were formulated, before behavioural activation was used to …

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

Faculty, Staff and Student Publications

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

Differential Behavioral Responses In Male And Female Mice Lacking Either Rgs2 Or Rgs4 Proteins After Acute Administration Of Antidepressants And Anxiolytics, Hiroyoshi Matsui, Sarah Seeley, Manoranjan S. D'Souza

ONU Student Research Colloquium

The overall objective of the study was to assess the acute behavioral effects of currently used antidepressants and anxiolytics in male and female mice lacking regulator of G protein-signaling (RGS) proteins 2 and 4 and their wild-type counterparts. RGS 2 and 4 proteins negatively modulate signaling pathways of G protein-coupled receptors (GPCRs), which play an important role in mediating the effects of monoamine neurotransmitters such as dopamine, norepinephrine, and serotonin. These neurotransmitters in turn play an important role in the action of antidepressant and anxiolytic medications. The study was undertaken because no studies till date have systematically assessed the behavioral …

Linear And Nonlinear Behaviors Of The Photoreceptor Coupled Network, Ji-Jie Pang, Xiaolong Jiang, Samuel M Wu

Faculty, Staff and Students Publications

Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study, we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to eight cells and …

Multicenter Us Clinical Experience With The Scepter Mini Balloon Catheter, Mohamed M Salem, Paz Kelmer, Georgios S Sioutas, Sophie Ostmeier, Alex Hoang, Gustavo Cortez, Kareem El Naamani, Rawad Abbas, Ricardo Hanel, Omar Tanweer, Visish M Srinivasan, Pascal Jabbour, Peter Kan, Brian T Jankowitz, Jeremy J Heit, Jan-Karl Burkhardt

Faculty, Staff and Students Publications

INTRODUCTION: Distal navigability and imprecise delivery of embolic agents are two limitations encountered during liquid embolization of cerebrospinal lesions. The dual-lumen Scepter Mini balloon (SMB) microcatheter was introduced to overcome these conventional microcatheters' limitations with few small single-center reports suggesting favorable results.

METHODS: A series of consecutive patients undergoing SMB-assisted endovascular embolization were extracted from prospectively maintained registries in seven North-American centers (November 2019 to September 2022).

RESULTS: Fifty-four patients undergoing 55 embolization procedures utilizing SMB were included (median age 58.5; 48.1% females). Cranial dural arteriovenous fistula embolization was the most common indication (54.5%) followed by cranial arteriovenous malformation (27.3%). …

Novel Approach To Difficult Spinal Reconstruction: Bilateral Simultaneous Rib And Iliac Crest Vascularized Bone Graft Spinoplastic Surgery, Maria Shvedova, Isra Abdulwadood, Daniel M Vernik, Max A Shrout, Jonathan L Jeger, Dylon C Buchanan, Alexander Ropper, Sebastian Winocour, Michael Bohl, Maziyar A Kalani, Edward M Reece

Faculty, Staff and Students Publications

Pseudoarthrosis is a severe complication of spinal fusion surgery with occurrence rates as high as 35%-40%. Current options of revision surgery to correct pseudoarthrosis frequently carry high failure rates and risk of developing junctional kyphosis. Pedicled vascularized bone grafts (VBGs) are an innovative approach to boost spinal fusion rates via improving structural integrity and increasing the delivery of blood to the donor site. This versatile technique can be performed at different spinal levels without additional skin incisions and with minimal added operative time. Here we present the first bilateral rib and iliac crest VBG spinoplastic surgery performed to augment spinal …

Consensus On Best Practices In Neuroscience-Informed Treatment Of Combat-Related Posttraumatic Stress In Military Veterans: A Delphi Study Of Experts In The Field Of Mental Health, Danielle Lauren Winters

Counseling & Human Services Theses & Dissertations

The purpose of this study was to capture consensus among mental health professionals who work with combat trauma-afflicted veterans and/or utilize a neuroscience-informed counseling approach, about a set of best practices for uniting neuroscience-informed treatment modalities with the treatment of veterans who present with Post Traumatic Stress (PTS). A multi-round Delphi study was used to elicit information from mental health professionals, which led to the proposition of ways in which mental health professionals may more efficiently work with combat veterans while utilizing neuroscience-informed treatments such as Prolonged Exposure Therapy, Eye Movement Desensitization and Reprocessing (EMDR) neuro-informed Cognitive Behavioral therapy (nCBT), …

A Therapeutically Targetable Positive Feedback Loop Between Nc-Hlx-2-7, Hlx, And Myc That Promotes Group 3 Medulloblastoma, Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse …

Ongoing Study Of The Association Of Apoe Gene Polymorphisms With Cognitive Impairment In The Rio Grande Valley Hispanic Population, Jaime Miguel L. Saveron, Daniela Gamez, Chun Xu

Research Symposium

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, exhibits a significant genetic component. In addition, mild cognitive impairment (MCI) is a key risk factor for AD. While certain demographic factors and genetic variants associated with AD and cognitive impairment have been identified in non-Hispanic populations, limited research exists on this subject within the Hispanic population, particularly in the Rio Grande Valley. This study aims to investigate the relationship between the APOE gene, specifically its ε4 allele, and cognitive impairment in the Hispanic population of the Rio Grande Valley.

Methods: A total of 269 Hispanic subjects, aged 60 and above, with …

Childhood Cancer Mutagenesis Caused By Transposase-Derived Pgbd5, Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, Daniel Cameron, Hiromichi Suzuki, Reeti Sanghrajka, Jake Vaynshteyn, Jeffrey Gerwin, Francesco Maura, William Hooper, Minita Shah, Nicolas Robine, Phillip Demarest, N Sumru Bayin, Luz Jubierre Zapater, Casie Reed, Steven Hébert, Ignas Masilionis, Ronan Chaligne, Nicholas D Socci, Michael D Taylor, Claudia L Kleinman, Alexandra L Joyner, G Praveen Raju, Alex Kentsis

Faculty, Staff and Students Publications

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development. Ectopic activation of SHH signaling is sufficient to enforce cerebellar granule cell progenitor-like cell states, which exhibit Pgbd5-dependent expression of distinct DNA repair and neurodevelopmental factors. Mouse medulloblastomas expressing Pgbd5 have increased numbers of somatic structural DNA rearrangements, …

Gamma-Aminobutyric Acid (Gaba) Neurons And Perineuronal Nets (Pnn) In The Monodelphis Domestica And Relevance To Psychiatric Disorders, Jatziry Z. Luna Escobedo, Mariela Garcia, John L. Vandeberg, Mario Gil

Research Symposium

Background/ Purpose: Gamma-aminobutyric acid (GABA) is an amino acid that serves as the central nervous system’s (CNS) main inhibitory neurotransmitter. By inhibiting nerve transmission, it works to lower neuronal excitability. Altered GABA levels have been associated with a variety of psychiatric disorders, for example Epilepsies, Parkinson’s Disease, and Schizophrenia. Perineuronal nets (PNN) are extracellular molecules that are released by neurons and glial cells that modulate many neuronal and glial functions by encapsulating the inhibitory cells and neurites. Altered PNN levels serve as a potential trigger to synaptic imbalance. The purpose of this study is to quantify and analyze the presence, …

Brain-Specific Serine/Threonine-Protein Kinase 1 Is A Substrate Of Protein Kinase C Epsilon Involved In Sex-Specific Ethanol And Anxiety Phenotypes, Michael P. Dugan, Rajani Maiya, Caleb Fleischer, Michal Bajo, Angela E. Snyder, Ashwin Koduri, Sathvik Srinivasan, Marisa Roberto, Robert O. Messing

School of Graduate Studies Faculty Publications

Protein kinase C epsilon (PKCε) regulates behavioural responses to ethanol and plays a role in anxiety-like behaviour, but knowledge is limited on downstream substrates of PKCε that contribute to these behaviours. We recently identified brain-specific serine/threonine-protein kinase 1 (BRSK1) as a substrate of PKCε. Here, we test the hypothesis that BRSK1 mediates responses to ethanol and anxiety-like behaviours that are also PKCε dependent. We used in vitro kinase assays to further validate BRSK1 as a substrate of PKCε and used Brsk1−/− mice to assess the role of BRSK1 in ethanol- and anxiety-related behaviours and in physiological responses to ethanol. We …

Distributed Neural Representations Of Conditioned Threat In The Human Brain, Zhenfu Wen, Edward F Pace-Schott, Sara W Lazar, Jörgen Rosén, Fredrik Åhs, Elizabeth A Phelps, Joseph E Ledoux, Mohammed R Milad

Faculty, Staff and Student Publications

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety …

Heterogeneity And Overlap In The Continuum Of Linguistic Profile Of Logopenic And Semantic Variants Of Primary Progressive Aphasia: A Profile Analysis Based On Multidimensional Scaling Study, Gaia Chiara Santi, Francesca Conca, Valentina Esposito, Cristina Polito, Silvia Paola Caminiti, Cecilia Boccalini, Carmen Morinelli, Valentina Berti, Salvatore Mazzeo, Valentina Bessi, Alessandra Marcone, Sandro Iannaccone, Se-Kang Kim, Sandro Sorbi, Daniela Perani, Stefano F Cappa, Eleonora Catricalà

Faculty, Staff and Students Publications

BACKGROUND: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce.

METHODS: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [

RESULTS: Patients' profiles were distributed across a …

Factors Affecting Selection Of Trainee For Neurointervention (Fasten), Mohamed Elfil, Rami Z Morsi, Sherief Ghozy, Ahmed Elmashad, Adnan Siddiqui, Alhamza R Al-Bayati, Ali Alaraj, Allan Brook, Anthony W Kam, Arindam Rano Chatterjee, Athos Patsalides, Ben Waldau, Charles J Prestigiacomo, Charles Matouk, Clemens M Schirmer, David Altschul, David T Parrella, Gabor Toth, Gaurav Jindal, Hamza A Shaikh, Jaydevsinh N Dolia, Johanna T Fifi, Justin F Fraser, Justin Thomas Do, Krishna Amuluru, Louis J Kim, Mark Harrigan, Matthew R Amans, Max Kole, Max Mokin, Michael Abraham, Mouhammad Jumaa, Nazli Janjua, Osama Zaidat, Patrick P Youssef, Priyank Khandelwal, Qingliang Tony Wang, Ramesh Grandhi, Ricardo Hanel, Ryan T Kellogg, Santiago Ortega-Gutierrez, Sunil Sheth, Thanh N Nguyen, Viktor Szeder, Yin C Hu, Albert J Yoo, Omar Tanweer, Brian Jankowitz, Jeremy J Heit, Richard Williamson, Tareq Kass-Hout, Richard W Crowley, Mohammad El-Ghanem, Fawaz Al-Mufti

Faculty, Staff and Students Publications

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process.

METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. …

Uchl1 Is A Potential Molecular Indicator And Therapeutic Target For Neuroendocrine Carcinomas, Shiqin Liu, Timothy Chai, Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu, Michelle Shen, Angus Martin Shaw Toland, Abel Bermudez, Alifiani B Hartono, Christopher F Massey, Chung S Lee, Liwei Zheng, Maya Baron, Caden J Denning, Merve Aslan, Holly M Nguyen, Rosalie Nolley, Amina Zoubeidi, Millie Das, Christian A Kunder, Brooke E Howitt, H Tom Soh, Irving L Weissman, Michael A Liss, Arnold I Chin, James D Brooks, Eva Corey, Sharon J Pitteri, Jiaoti Huang, Tanya Stoyanova

Faculty, Staff and Student Publications

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of …

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 …

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 …

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 …

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 …

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 …

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 …

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.

Comparative Transcriptomic Analysis Of Cerebellar Astrocytes Across Developmental Stages And Brain Regions, Wookbong Kwon, Dong-Joo Choi, Kwanha Yu, Michael R Williamson, Sanjana Murali, Yeunjung Ko, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expressed genes (DEGs) published for the cortex, hippocampus, and olfactory bulb revealed cerebellar-specific gene signature across these …

Single-Cell Multi-Omic Analysis Of The Vestibular Schwannoma Ecosystem Uncovers A Nerve Injury-Like State, Thomas F Barrett, Bhuvic Patel, Saad M Khan, Riley D Z Mullins, Aldrin K Y Yim, Sangami Pugazenthi, Tatenda Mahlokozera, Gregory J Zipfel, Jacques A Herzog, Michael R Chicoine, Cameron C Wick, Nedim Durakovic, Joshua W Osbun, Matthew Shew, Alex D Sweeney, Akash J Patel, Craig A Buchman, Allegra A Petti, Sidharth V Puram, Albert H Kim

Faculty, Staff and Students Publications

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq (n = 6) and exome sequencing (n = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, …

Multi-Site Benchmark Classification Of Major Depressive Disorder Using Machine Learning On Cortical And Subcortical Measures, Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R K Ching, Colm G Connolly, Kathryn Cullen, Christopher G Davey, Danai Dima, Annemiek Dols, Jennifer W Evans, Cynthia H Y Fu, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke Groenewold, J Paul Hamilton, Ben J Harrison, Tiffany C Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Elisa Melloni, Bryon A Mueller, Amar Ojha, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Elena Pozzi, Liesbeth Reneman, Matthew D Sacchet, Philipp G Sämann, Anouk Schrantee, Kang Sim, Jair C Soares, Dan J Stein, Sophia I Thomopoulos, Aslihan Uyar-Demir, Nic J A Van Der Wee, Steven J A Van Der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Roberto Goya-Maldonado, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy …

The Immune System And Metabolic Products In Epilepsy And Glioma-Associated Epilepsy: Emerging Therapeutic Directions, Shashwat Tripathi, Cody L Nathan, Matthew C Tate, Craig M Horbinski, Jessica W Templer, Joshua M Rosenow, Timothy L Sita, Charles D James, Benjamin Deneen, Stephen D Miller, Amy B Heimberger

Faculty, Staff and Students Publications

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. …

Developmental Basis Of Shh Medulloblastoma Heterogeneity, Maxwell P Gold, Winnie Ong, Andrew M Masteller, David R Ghasemi, Julie Anne Galindo, Noel R Park, Nhan C Huynh, Aneesh Donde, Veronika Pister, Raul A Saurez, Maria C Vladoiu, Grace H Hwang, Tanja Eisemann, Laura K Donovan, Adam D Walker, Joseph Benetatos, Christelle Dufour, Livia Garzia, Rosalind A Segal, Robert J Wechsler-Reya, Jill P Mesirov, Andrey Korshunov, Kristian W Pajtler, Scott L Pomeroy, Olivier Ayrault, Shawn M Davidson, Jennifer A Cotter, Michael D Taylor, Ernest Fraenkel

Faculty, Staff and Students Publications

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different …