Neurosciences Commons^™

Role Of Bevacizumab In Multiple Glioblastomas: A Retrospective Single-Center Analysis, Yongrui Zhao, Yidong Chen, Leiming Wang, Ye Cheng, Feng Yan, Jiankun Xu

Neurosciences

Objective: To explore the prognostic factors of multiple glioblastomas (M-GBMs) and the role of bevacizumab (BEV) in M-GBMs. Methods: 162 patients treated for primary glioblastoma (GBM) from 2020 to 2024 were retrospectively reviewed. Kaplan–Meier analysis was performed to compare progression-free survival (PFS) and overall survival (OS) between the single glioblastoma (S-GBM) group and the M-GBMs group. Independent predictors of OS among M-GBMs patients were evaluated via multivariable Cox regression analysis. Results: 116 patients had S-GBM, and 46 had M-GBMs. Compared with S-GBM patients, M-GBMs patients had poorer PFS (6.5 vs. 11 months, p<0.001) and OS (15.5 vs. 21 months, p=0.005). In the M-GBMs group, based on the RANO resection criteria, both univariable analysis and multivariable Cox models confirmed that the extent of resection, use of radiotherapy and chemotherapy, p53 overexpression, and use of BEV were all factors that significantly influenced OS. Specifically, the use of BEV prolonged OS from 12 months to 19.5 months (p = 0.017). From the initiation of BEV therapy, the median PFS was 5.5 months (95% CI 4.45–6.56 months), and the median survival was significantly longer than in those who did not received BEV (10 vs. 3 months, p = 0.021). Conclusion: The extent of resection, radiotherapy/chemotherapy, p53 …

Lateral Habenula And Dorsal Raphe Neurons Signal Value Computations In Multi-Attribute Decision-Making, Yang-Yang Feng

McKelvey School of Engineering Graduate Student Theses & Dissertations

Decision-making is a fundamental part of adaptive behavior and can be compromised in psychiatric illness. Humans and animals are continuously presented with objects and opportunities as options to decide between. One challenge is that these options may independently vary along multiple dimensions or attributes that we care about. This can include attributes of physical reward, such as amount, delay, or uncertainty. When these attributes are present, the possibility of an abstract, cognitive reward, advance information to resolve uncertainty, may also motivate our decisions. It is unclear how the brain makes these subjective decisions, trading off between these multiple attributes based …

Functional And Spatially Specialized Inhibition And Neuromodulation During Learning In The Hippocampus, Gerardo Enrique Molina

McKelvey School of Engineering Graduate Student Theses & Dissertations

The hippocampus relies on a diverse network of regulatory components for memory formation. Neuromodulators and inhibitory interneurons act in concert with excitatory neurons to control learning. Even within one of these components there is a vast diversity of genetic or chemical composition that may come from unique sources at uniquely timed intervals or events. The goal of this dissertation is to identify specific functional-behavioral attributes of two such examples: parvalbumin (PV)-expressing interneurons and the neuromodulator dopamine, in hippocampal CA1. In separate experiments, I used two-photon microscopy of the calcium sensor, GCaMP, which measures neuronal activity, and GRAB-DA, which reports levels …

Eeg Studies Of Pre-Stimulus Activity During Turn-Taking In Naturalistic Conversation, Seyedmohamadreza Manzourolajdad

Student Works (2020-2029)

This study integrates conversational analysis principles and neural activity to investigate natural cognition and examine event-related brain changes. A wireless electroencephalography (EEG) device was used in an ecological validity setting to analyse pre-stimulus brain activity preceding conversational turns. This study aims to identify aspects of the conversation that reflect its naturalness in the aspect of listening and the corresponding brain activity by analysing the signals before and after a turn in a conversation. This research contributes to an ecologically valid understanding of natural conversation as a social action that enables seamless communication. Seven Malaysian participants (aged 19–22, M=20.46) engaged in …

Disruption Of The Lrrk2 Substrate Rab12 Facilitates Neurotransmission And Causes Hyperactivity In Mice, Xingjian Li, Yuanxin Chen, Huaixing Wang, Xue Zhang, Noah Guy Lewis Guiberson, Xianting Li, Jacqueline Burré, Junmin Peng, Hui Zhang, Zhenyu Yue

Department of Neuroscience Faculty Papers

RAB12 is a small GTPase and a validated substrate of LRRK2, a kinase genetically linked to Parkinson's disease (PD). While RAB12-LRRK2 signaling has been implicated in ciliogenesis and immune regulation, the neuronal function of RAB12 remains largely unexplored. Here, we investigated the role of RAB12 in synaptic physiology using Rab12 knockout (KO) mice. Rab12 KO mice developed normally but exhibited increased locomotor activity in adulthood. Electrophysiological recordings from striatal slices revealed enhanced presynaptic release probability and increased excitatory drive onto medium spiny neurons. Consistently, live-cell imaging of cultured cortical neurons revealed that Rab12 deletion facilitated, while Rab12 overexpression inhibited, synaptic …

Investigating Sertraline‑Mediated Modulation Of Succinate Dehydrogenase To Sensitize Tmz‑Resistant Glioblastoma Cells, Supraja Mallapuram

Create@State

Glioblastoma (GBM) is one of the deadliest and most common brain tumor which remains highly resistant to temozolomide (TMZ), contributing to poor patient outcomes. Literature suggests that sertraline, a widely used SSRI, disrupts mitochondrial metabolism in cancer cells. Because GBM depends heavily on succinate dehydrogenase (SDH) for oxidative phosphorylation, sertraline‑mediated SDH inhibition may increase metabolic stress and reduce functional TMZ resistance. This poster presents a literature‑based rationale and proposed experimental design to evaluate sertraline‑induced SDH modulation and its potential to sensitize TMZ‑resistant T98G glioblastoma cells. These findings will guide future experimental work.

Astrocyte Circadian Regulation In Neurodegeneration: In Vivo Bmal1 Occupancy Mapping Using Macs-Calling Cards, India Reiss

Arts & Sciences Graduate Student Theses and Dissertations

Astrocytes maintain neuronal homeostasis through cellular programs that are frequently disrupted early in neurodegenerative disease, many of which are regulated by the circadian clock. The core clock transcription factor BMAL1 is required for normal astrocyte function, yet whether its regulatory activity is altered during neurodegeneration remains unclear. BMAL1 expression changes in disease are often inconsistent, suggesting that transcription factor binding, rather than expression, may be a more informative readout of BMAL1 function. We used a Cln3Δex7/8 model of neurodegeneration, which exhibits early astrocyte dysfunction prior to widespread neuronal loss, to test whether degenerative pathology reprograms BMAL1 binding in astrocytes. We …

Conserved Post-Odor Dynamics In The Olfactory Systems Of Mice And Locusts, Elizabeth H Moss, Doris Ling, Cameron L Smith, Feiyang Deng, Ryan Kroeger, Jacob Reimer, Baranidharan Raman, Benjamin R Arenkiel

Faculty, Staff and Students Publications

Interpreting chemical information and translating it into ethologically relevant output is a shared challenge of olfactory systems across species, but are olfactory computations conserved across species to overcome these common challenges? To investigate this, we compared neural activity in the locust antennal lobe (AL) and mouse olfactory bulb (OB) both during and after odor presentations. We found that odors activated nearly mutually exclusive neural ensembles during odor presentations ("ON response") and after the termination of the odor stimulus ("OFF response"). ON and OFF responses evoked by a single odor were anticorrelated with each other. Inverted OFF responses persisted long after …

Convergent Rna Pathophysiology In Amyotrophic Lateral Sclerosis, Hunter Lee Patterson

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation explores the connection between amyotrophic lateral sclerosis pathogenesis and RNA biology via two mechanisms: microRNA regulation of gene expression in the spinal cord and modulation of TDP-43 pathology through synthetic oligonucleotides. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of motor neurons in the brain and spinal cord that leads to progressive weakness. However, despite this shared clinical pattern the known causes of ALS are extremely varied. Only about 10% of ALS cases are familial while the other 90% occur sporadically. Even among that small fraction of familial cases, researchers have identified dozens …

Spontaneous Blood Oxygen Level Dependent Signals In Glioblastoma-Bearing And Aging Brains, Ki Yun Park

Arts & Sciences Graduate Student Theses and Dissertations

Brain activity fluctuates across timescales from microseconds to decades, reflecting processes ranging from rapid synaptic transmission to slow neuromodulatory and homeostatic changes. Resting-state functional magnetic resonance imaging (rs-fMRI) captures the slow end of this spectrum (spontaneous blood oxygen level-dependent (BOLD) fluctuations over tens to hundreds of seconds), which reflect the integrated output of these underlying processes and are increasingly recognized as sensitive to both pathological and physiological brain states. The core of this thesis examines rs-fMRI as a biomarker for two clinical entities: glioblastoma and aging. Reliable biomarker development requires both methodological rigor and analytic breadth, knowing what the method …

To Seize Or Not To Seize? That Is The (Epigenetic) Question, Corey St Romain, Jeannie Chin

Faculty, Staff and Students Publications

No abstract provided.

Evaluating The Utility Of Rnaseq In Prenatal Diagnostics: Expression Profiles Of Cultured Chorionic Villus And Amniotic Fluid Samples, Maria C Vladoiu, Sen Zhao, Roni Zemet, Christian M Parobek, Jefferson Cruz Sinson, Stacy Tankersley, Ignatia B Van Den Veyver, Pengfei Liu

Duncan NRI Faculty and Staff Publications

Objective: While RNAseq has enhanced variant interpretation in postnatal cases, its potential in the prenatal setting remains underexplored. This study investigates the utility of RNAseq in prenatal diagnostics by analyzing the expression profiles of cultured chorionic villus samples (cCVS) and amniotic fluid (cAF) samples.

Methods: We performed RNAseq on 25 prenatal samples (10 cCVS and 15 cAF) and compared their expression profiles with those of postnatal tissues-blood and skin fibroblasts.

Results: To evaluate the clinical relevance of gene expression in these samples, we curated a list of genes associated with fetal-onset genetic disorders (n = 375). Using this curated list …

Protocol For Inducing Focal Striatal Stroke In Mice Using Photothrombosis, Bridget R. Boyle, Eileen Collyer, Andrea P. Berghella, Elena Blanco-Suarez

Department of Neuroscience Faculty Papers

Here, we present a protocol for inducing focal striatal stroke in mice using photothrombosis. We describe steps for photothrombotic striatal surgery, magnetic resonance imaging, open field behavioral assessment of stroke-induced motor deficits, and post-stroke monitoring. We then detail procedures for tissue collection and immunofluorescence. This protocol provides a standardized approach for consistently modeling striatal stroke in mice, enabling mechanistic studies and preclinical therapeutic testing.

Improving Anesthesia Provider Confidence In The Identification, Management, And Treatment Of Postoperative Delirium, Brittany M. Whistle, Charles Dustin Phelps

Scholars Week

Purpose: Postoperative Delirium (POD) is a potentially devastating complication of anesthesia that is poorly understood by clinical staff leading to poor outcomes for surgical patients. This study is meant to determine if a focused knowledge presentation accompanied by visual aids could increase anesthesia providers confidence in identifying, diagnosing, and treating Postoperative Delirium.

Methodology: Utilizing a statistical model to analyze respondents results on a standardized test administered before and after an informational presentation with visual aids on the topic of Postoperative Delirium.

Results: Results indicated a statistically significant difference between pretest and posttest scores, with a p-value of .002, t(11) = …

Feeding The Mind: Dietary Consumption And Neural Aging, Bhavani Tuppale

Senior Theses

Neural aging is the process of physiological decline in the brain and increased vulnerability to neurodegenerative diseases. Neurodegenerative diseases such as Alzheimer’s disease are associated with aging and the interaction of genetics and lifestyle choices. Previous research studies have connected Alzheimer’s disease with dysfunction in the metabolic system. To combat age-associated dysfunctions in the metabolic system, research studies propose using the ketogenic diet, which utilizes ketone bodies as an energy source instead of glucose. The thesis analyzes literature on the effect of neural aging on various model organisms, how a ketogenic diet affects aging model organisms, and how aging and …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Efficient In Vivo Pharmacological Inhibition Of Δfosb, An Ap-1 Transcription Factor, In The Brain, Sean Mcneme, Anil Kumar, Yun Young Yim, Brandon W Hughes, Corey St Romain, Yi Li, Ashwani Kumar, Qichao Bao, Molly Estill, Shanghua Fan, Nadeen Takatka, Earnest P Chen, Matthew Rivera, Haiying Chen, Alfred J Robison, Mischa Machius, Stephen J Haggarty, Jeannie Chin, Eric J Nestler, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, an unusually stable member of the AP-1 family of transcription factors, mediates long-term maladaptations that play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesia, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitro in cell-based assays, and one such compound, JPC0661, disrupts ΔFOSB binding to genomic DNA in vivo in the mouse brain with partial efficiency. JPC0661 binds to a groove outside of the DNA-binding cleft of the ΔFOSB/JUND bZIP heterodimer in a cocrystal structure. Here, we generated a …

Author Correction: Foundation Model Of Neural Activity Predicts Response To New Stimulus Types, Eric Y Wang, Paul G Fahey, Zhuokun Ding, Stelios Papadopoulos, Kayla Ponder, Marissa A Weis, Andersen Chang, Taliah Muhammad, Saumil Patel, Zhiwei Ding, Dat Tran, Jiakun Fu, Casey M Schneider-Mizell, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa, Katrin Franke, Alexander S Ecker, Jacob Reimer, Xaq Pitkow, Fabian H Sinz, Andreas S Tolias

Faculty, Staff and Students Publications

This corrects the article "Foundation model of neural activity predicts response to new stimulus types" in volume 640 on page 470.

Author Correction: Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Astrazeneca Genomics Initiative, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

No abstract provided.

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …