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Full-Text Articles in Neurosciences

Investigating Sertraline‑Mediated Modulation Of Succinate Dehydrogenase To Sensitize Tmz‑Resistant Glioblastoma Cells, Supraja Mallapuram Apr 2026

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.


The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego Jan 2026

The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego

Biological Sciences Faculty Publications

Postsynaptic scaffolding protein SAP90/PSD95-associated protein 3 (SAPAP3) modulates cortico-striatal signalling and regulates the maintenance of synaptic structure. Notably, SAPAP3 defects have been reported in several human psychiatric disorders that share pathophysiological features with Huntington’s disease (HD), a neurodegenerative disorder characterized by the expression of mutant huntingtin (mHTT) and marked dysfunction of cortico-striatal synapses and mitochondria. However, the role of SAPAP3 in mitochondrial function and HD pathophysiology remains unexplored. SAPAP3 was extracted from striatal synaptoneurosomes and analyzed by SWATH-MS proteomics to identify potential interactors, revealing SAPAP3 association with several mitochondrial proteins, particularly Mic60. These data were further complemented with proximity ligation …


Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills Aug 2025

Prior Adolescent Oxycodone Exposure Enhances Pain Sensitivity Following Chronic Intermittent Ethanol In Adult Female Mice, Lisa L. Wilson, Lucas Albrechet-Souza, Linh Ha, Nicholas W. Gilpin, Tiffany A. Wills

School of Graduate Studies Faculty Publications

The opioid crisis remains a critical public health concern, with rising rates of overdose and opioid use disorder. While opioids are effective for managing pain, both chronic use and withdrawal are associated with increased pain sensitivity. Although most prior research has focused on adults, opioid use during adolescence is common and linked to a heightened risk for developing alcohol use disorder and other forms of substance misuse. Like opioids, acute alcohol use can be analgesic, but chronic alcohol exposure and withdrawal lead to increased pain sensitivity. However, the interactive effects of adolescent opioid and adult alcohol exposure on pain remain …


Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah Jan 2025

Optimizing Decision-Making In A Cerebral Palsy Model Using Reinforcement Learning, Richard Ampah

Pitzer Senior Theses

This study presents an original interdisciplinary investigation into how reinforcement learning (RL) can model motor and cognitive defects and potentially improve motor and cognitive functions in individuals with cerebral palsy (CP), a non-progressive neurological disorder that impairs movement and adaptability. Integrating computational neuroscience and machine learning, the research applies policy gradient methods and Markov Decision Processes (MDPs) to simulate adaptive learning in agents with and without CP-related constraints.

The central aim is to compare the cumulative rewards of optimal policies, derived from value iteration, and human-like learning policies using the REINFORCE algorithm, both with and without the Bellman baseline. The …


Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan May 2024

Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan

School of Medicine Faculty Publications

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …


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 Mar 2024

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 …


Examining The Impact Of Firearm Recoil During A Round Of Trap Shooting On Neurometabolic Changes Associated With Traumatic Brain Injury, Lakota Jones Jan 2024

Examining The Impact Of Firearm Recoil During A Round Of Trap Shooting On Neurometabolic Changes Associated With Traumatic Brain Injury, Lakota Jones

Theses, Dissertations and Capstones

The CDC identifies concussion as a blunt, blow, or jolt to the head resulting in brain injury. Shooting sports do not impose a direct blow to the head but instead inflict rapid acceleration to the brain via recoil transfer. Exposure to rapid, repetitive recoil may cause physiological disturbances in the brain, therefore resulting in mild traumatic brain injury (TBI). Chronic recoil transfer and overpressure exposure influencing neurometabolic changes of TBI have yet to be measured. The objective of this study was to examine kinetic energy experienced in trap and skeet shooters following one round of shooting in comparison to neurometabolic …


Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White Jan 2024

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. A …


Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis Jan 2024

Synthetic Neuroactive Steroids Targeting Gaba-A Receptors As A Potential Therapy For Contraceptive-Associated Mood Disorders, Alexandria A. Davis

Scripps Senior Theses

4-10% of women who use hormonal oral contraceptives (HOCs) discontinue use after experiencing symptoms of anxiety, irritability, and depression in the first 3 months of administration. Previous studies have acknowledged a relationship between HOCs and emotional dysregulation but have not identified mechanisms by which HOCs have this effect. As a result, effective treatment options for HOC-induced mood disorders are lacking. Current theories implicate combined-HOCs, particularly those containing ethinyl estradiol and levonorgestrel (EE-LNG), in reducing neuroactive steroid levels. Specifically, HOC users show decreases in allopregnanolone, a positive allosteric modulator associated with neuronal inhibition and emotional regulation. The objective of this study …


Fundamental Neurochemistry Review: The Role Of Enteroendocrine Cells In Visceral Pain, Annie Londregan, Tyler D. Alexander, Manuel Covarrubias, Scott A. Waldman Dec 2023

Fundamental Neurochemistry Review: The Role Of Enteroendocrine Cells In Visceral Pain, Annie Londregan, Tyler D. Alexander, Manuel Covarrubias, Scott A. Waldman

Department of Neuroscience Faculty Papers

While visceral pain is commonly associated with disorders of the gut-brain axis, underlying mechanisms are not fully understood. Dorsal root ganglion (DRG) neurons innervate visceral structures and undergo hypersensitization in inflammatory models. The characterization of peripheral DRG neuron terminals is an active area of research, but recent work suggests that they communicate with enteroendocrine cells (EECs) in the gut. EECs sense stimuli in the intestinal lumen and communicate information to the brain through hormonal and electrical signaling. In that context, EECs are a target for developing therapeutics to treat visceral pain. Linaclotide is an FDA-approved treatment for chronic constipation that …


A Phenomenological Take On Mirror Self-Face Perception In Schizophrenia, Giovanni Pennisi Apr 2023

A Phenomenological Take On Mirror Self-Face Perception In Schizophrenia, Giovanni Pennisi

Journal of Mind and Medical Sciences

Studies concerning social deficits in schizophrenia has often been restrained to exploring facial recognition. Various investigations have shown that those diagnosed with schizophrenia have difficulties in perceiving the identities and emotions of those around them merely through observing their facial features. A few others have also taken into account the issue of self-face recognition in individuals with schizophrenia, finding that their capacity to associate photos or videos of their own face to themselves is hindered due to the illness. However, to my knowledge, only a few studies have so far delved into the intricacies of how individuals with schizophrenia or …


Massive Loss Of Proprioceptive Ia Synapses In Rat Spinal Motoneurons After Nerve Crush Injuries In The Postnatal Period, Ariadna Arbat-Plana, Sara Bolívar, Xavier Navarro, Esther Udina, Francisco J. Alvarez Feb 2023

Massive Loss Of Proprioceptive Ia Synapses In Rat Spinal Motoneurons After Nerve Crush Injuries In The Postnatal Period, Ariadna Arbat-Plana, Sara Bolívar, Xavier Navarro, Esther Udina, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries (PNIs) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from α-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed, and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. The goal of this study was to analyze …


Fast Blue And Cholera Toxin-B Survival Guide For Alpha-Motoneurons Labeling: Less Is Better In Young B6sjl Mice, But More Is Better In Aged C57bl/J Mice, Hasan Farid, Weston B. Gleford, Lori L. Goss, Teresa L. Garrett, Sherif M. Elbasiouny Jan 2023

Fast Blue And Cholera Toxin-B Survival Guide For Alpha-Motoneurons Labeling: Less Is Better In Young B6sjl Mice, But More Is Better In Aged C57bl/J Mice, Hasan Farid, Weston B. Gleford, Lori L. Goss, Teresa L. Garrett, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Fast Blue (FB) and Cholera Toxin-B (CTB) are two retrograde tracers extensively used to label alpha-motoneurons (α-MNs). The overall goals of the present study were to (1) assess the effectiveness of different FB and CTB protocols in labeling α-MNs, (2) compare the labeling quality of these tracers at standard concentrations reported in the literature (FB 2% and CTB 0.1%) versus lower concentrations to overcome tracer leakage, and (3) determine an optimal protocol for labeling α-MNs in young B6SJL and aged C57Bl/J mice (when axonal transport is disrupted by aging). Hindlimb muscles of young B6SJL and aged C57Bl/J mice were intramuscularly …


Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny Oct 2022

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …


A Case Of Intractable Hyperhidrosis In Spinal Cord Injury: Role Of Stellate Ganglion Block, Soun Sheen, Hemant Kalia, Victoria Kung Sep 2022

A Case Of Intractable Hyperhidrosis In Spinal Cord Injury: Role Of Stellate Ganglion Block, Soun Sheen, Hemant Kalia, Victoria Kung

Advances in Clinical Medical Research and Healthcare Delivery

Objective:

Autonomic dysreflexia (AD) in spinal cord injury (SCI) can present as hyperhidrosis due to sudomotor dysfunction. Hyperhidrosis can also occur without an identifiable etiology. There are no standard treatment guidelines for refractory hyperhidrosis in the setting of persistent noxious stimulation. Stellate ganglion blockade may prevent hyperhidrosis by inhibiting profound sympathetic surge and vasoconstriction.

Case:

58-year-old female with C7 ASIA-A quadriplegia was admitted to the hospital for episodes of profuse sweating in the setting of autonomic dysreflexia secondary to underlying T7-8 discitis. Despite conservative treatment of discitis, patient continued experience 50-60 episodes of profuse sweating daily. Stellate ganglion block was …


Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny Sep 2022

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …


Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak Sep 2022

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.


The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez Jun 2022

The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …


Il-10 And Tgf-Β Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox, Mike Castro, Thomas L. Brown, Nancy J. Bigley Jun 2022

Il-10 And Tgf-Β Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox, Mike Castro, Thomas L. Brown, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

Cardiac resident macrophages facilitate electrical conduction by interacting with cardiomyocytes via connexin-43 (Cx43) hemichannels. Cx43 is critical for impulse propagation and coordination between muscle contractions. Cardiomyocyte electrophysiology can be altered when coupled with noncardiomyocyte cell types such as M2c tissue-resident macrophages. Using cocultures of murine HL-1 cardiomyocytes and RAW 264.7 macrophages, we examined the hypothesis that cytokine signals, TGF-β1 and IL-10, upregulate Cx43 expression at points of contact between the two cell types. These cytokine signals maintain the macrophages in an M2c anti-inflammatory phenotype, mimicking cardiac resident macrophages. The electrophysiology of cardiomyocytes was examined using di-8-ANEPPS potentiometric dye, which reflects …


A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer May 2022

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …


Acute Oxygen-Sensing Via Mitochondria-Generated Temperature Transients In Rat Carotid Body Type I Cells, Ryan J. Rakoczy, Clay M. Schiebrel, Christopher N. Wyatt Apr 2022

Acute Oxygen-Sensing Via Mitochondria-Generated Temperature Transients In Rat Carotid Body Type I Cells, Ryan J. Rakoczy, Clay M. Schiebrel, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell “hypoxic signaling” may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells. Sub-micron distance measurements (TASK-1: 0.33 ± 0.04 µm, n = 47 vs TASK-3: 0.32 ± 0.03 µm, n = …


A Rodent Animal Model For Forelimb To Lower Jaw Reorganization In Primary Somatosensory Cortex (Si) Barrel Field, Violeta Pellicer Morata Apr 2022

A Rodent Animal Model For Forelimb To Lower Jaw Reorganization In Primary Somatosensory Cortex (Si) Barrel Field, Violeta Pellicer Morata

Theses and Dissertations (ETD)

The goal of this study is to examine mechanisms underlying cortical reorganization in rat primary somatosensory (SI) cortex that follows forelimb deafferentation. The majority of human patients suffering from limb loss or brachial plexus avulsion injury, as well as patients that receive brachial plexus anesthesia, report phantom limb sensations/pain which are often associated with cortical reorganization. Patients with upper-limb deafferentation report sensations of the missing hand during tactile stimulation of the face, and this phenomenon has been termed hand-to-face remapping. We sought to develop a rodent model of deafferentation; our model system is the rat SI cortex barrel field present …


The Anti-Inflammatory Agent Bindarit Attenuates The Impairment Of Neural Development Through Suppression Of Microglial Activation In A Neonatal Hydrocephalus Mouse Model, Eri Iwasawa, Farrah N. Brown, Crystal Shula, Fatima Kahn, Sang Hoon Lee, Temugin Berta, David R. Ladle, Kenneth Campbell, Francesco T. Mangano, June Goto Mar 2022

The Anti-Inflammatory Agent Bindarit Attenuates The Impairment Of Neural Development Through Suppression Of Microglial Activation In A Neonatal Hydrocephalus Mouse Model, Eri Iwasawa, Farrah N. Brown, Crystal Shula, Fatima Kahn, Sang Hoon Lee, Temugin Berta, David R. Ladle, Kenneth Campbell, Francesco T. Mangano, June Goto

Neuroscience, Cell Biology & Physiology Faculty Publications

Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy …


Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt Nov 2021

Ethanol And Opioids Do Not Act Synergistically To Depress Excitation In Carotid Body Type I Cells, Ryan J. Rakoczy, Kajal Kamra, Yoon-Jae Yi, Christopher N. Wyatt

Neuroscience, Cell Biology & Physiology Faculty Publications

The combination of opioids and ethanol can synergistically depress breathing and the acute ventilatory response to hypoxia. Multiple studies have shown that the underlying mechanisms for this may involve calcium channel inhibition in central neurons. But we have previously identified opioid receptors in the carotid bodies and shown that their activation inhibits calcium influx into the chemosensitive cells. Given that the carotid bodies contribute to the drive to breathe and underpin the acute hypoxic ventilatory response, we hypothesized that ethanol and opioids may act synergistically in these peripheral sensory organs to further inhibit calcium influx and therefore inhibit ventilation.

Methods …


Genetic Targeting Of Adult Renshaw Cells Using A Calbindin 1 Destabilized Cre Allele For Intersection With Parvalbumin Or Engrailed1, Alicia R. Lane, Indeara C. Cogdell, Thomas M. Jessell, Jay B. Bikoff, Francisco J. Alvarez Oct 2021

Genetic Targeting Of Adult Renshaw Cells Using A Calbindin 1 Destabilized Cre Allele For Intersection With Parvalbumin Or Engrailed1, Alicia R. Lane, Indeara C. Cogdell, Thomas M. Jessell, Jay B. Bikoff, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Renshaw cells (RCs) are one of the most studied spinal interneurons; however, their roles in motor control remain enigmatic in part due to the lack of experimental models to interfere with RC function, specifically in adults. To overcome this limitation, we leveraged the distinct temporal regulation of Calbindin (Calb1) expression in RCs to create genetic models for timed RC manipulation. We used a Calb1 allele expressing a destabilized Cre (dgCre) theoretically active only upon trimethoprim (TMP) administration. TMP timing and dose influenced RC targeting efficiency, which was highest within the first three postnatal weeks, but specificity was low with …


Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak Oct 2021

Nsaids Naproxen, Ibuprofen, Salicylate, And Aspirin Inhibit Trpm7 Channels By Cytosolic Acidification, Rikki Chokshi, Orville Bennett, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Non-steroidal anti-inflammatory drugs (NSAIDs) are used for relieving pain and inflammation accompanying numerous disease states. The primary therapeutic mechanism of these widely used drugs is the inhibition of cyclooxygenase 1 and 2 (COX1, 2) enzymes that catalyze the conversion of arachidonic acid into prostaglandins. At higher doses, NSAIDs are used for prevention of certain types of cancer and as experimental treatments for Alzheimer’s disease. In the immune system, various NSAIDs have been reported to influence neutrophil function and lymphocyte proliferation, and affect ion channels and cellular calcium homeostasis. Transient receptor potential melastatin 7 (TRPM7) cation channels are highly expressed in …


Role Of Emotional Intelligence In Job Performance Of Healthcare Providers Working In Public Sector Hospitals Of Pakistan, Nimra Zaman, Khalida Naz Memon, Faryal Zaman, Komal Zaman Khan, Shazia Rahman Shaikh Oct 2021

Role Of Emotional Intelligence In Job Performance Of Healthcare Providers Working In Public Sector Hospitals Of Pakistan, Nimra Zaman, Khalida Naz Memon, Faryal Zaman, Komal Zaman Khan, Shazia Rahman Shaikh

Journal of Mind and Medical Sciences

Objective. To determine the association between emotional intelligence (EI) and job performance (JP) of health care providers (HCPs). Methods. Healthcare professionals from various hospitals were chosen for a cross-sectional study. The survey was conducted using a three-part questionnaire including the demographic profile, Wong and Law Emotional Intelligence (EI) Scale, and an individual work performance (JP) questionnaire. The relationship of predictor variables on JP was sought by applying Chi-square test and multiple regression analysis. Results. About 43.3% of the 50.8% of participants who scored well on the EI scale also scored high on the JP scales. The remaining …


Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson Sep 2021

Placenta-Specific Slc38a2/Snat2 Knockdown Causes Fetal Growth Restriction In Mice, Owen R. Vaughan, Katarzyna Maksym, Elena Silva, Kenneth Barentsen, Russel V. Anthony, Sara L. Hillman, Thomas L. Brown, Rebecca Spencer, Anna L. David, Fredrick J. Rosario, Theresa L. Powell, Thomas Jansson

Neuroscience, Cell Biology & Physiology Faculty Publications

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of …


Intensity-Dependent Changes In Quantified Resting Cerebral Perfusion With Multiple Sessions Of Transcranial Dc Stimulation, Matthew Sherwood, Lindsey Mcintire, Aaron T. Madaris, Kamin Kim, Charan Ranganath, R. Andy Mckinley Aug 2021

Intensity-Dependent Changes In Quantified Resting Cerebral Perfusion With Multiple Sessions Of Transcranial Dc Stimulation, Matthew Sherwood, Lindsey Mcintire, Aaron T. Madaris, Kamin Kim, Charan Ranganath, R. Andy Mckinley

Neuroscience, Cell Biology & Physiology Faculty Publications

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before …


Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown Jul 2021

Current State Of Preeclampsia Mouse Models: Approaches, Relevance, And Standardization, Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown

Neuroscience, Cell Biology & Physiology Faculty Publications

Preeclampsia (PE) is a multisystemic, pregnancy-specific disorder and a leading cause of maternal and fetal death. PE is also associated with an increased risk for chronic morbidities later in life for mother and offspring. Abnormal placentation or placental function has been well-established as central to the genesis of PE; yet much remains to be determined about the factors involved in the development of this condition. Despite decades of investigation and many clinical trials, the only definitive treatment is parturition. To better understand the condition and identify potential targets preclinically, many approaches to simulate PE in mice have been developed and …