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Articles 1 - 30 of 40
Full-Text Articles in Neurosciences
Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper
Rebound Bursting Selectively Enables Fast Dynamics In Dopamine Midbrain Neurons Projecting To The Dorsolateral Striatum, Strahinja Stojanovic, Christopher J. Knowlton, Richard Egger-Mackrodt, Johanna Mankel, Josef Shin, Stephan Lammel, Carmen C. Canavier, Jochen Roeper
School of Graduate Studies Faculty Publications
Dopamine (DA) midbrain neurons are involved in a wide array of key brain functions including movement control and reward-based learning. They are also critical for major brain disorders such as Parkinson's disease or schizophrenia. DA neurons projecting to distinct striatal territories are diverse with regard to their molecular makeup and cellular physiology, which are likely to contribute to the observed differences in temporal DA dynamics. Among these regions, the dorsolateral striatum (DLS) displays the fastest DA dynamics, which might control the moment-to-moment vigor and variability of voluntary movements. However, the underlying mechanisms for these DLS-specific fast DA fluctuations are unresolved. …
Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim
Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim
School of Graduate Studies Faculty Publications
During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic) neurons, cortical layer-specific cell …
A Single Center Study Of The Symbol Digit Modalities Test As A Screening Tool For Cognitive Impairment In Parkinson’S Disease, Daniyell Thomason, Morganne Manuel, Shannin Moody, Jesus Lovera, Brain Copeland, Deidre Devier
A Single Center Study Of The Symbol Digit Modalities Test As A Screening Tool For Cognitive Impairment In Parkinson’S Disease, Daniyell Thomason, Morganne Manuel, Shannin Moody, Jesus Lovera, Brain Copeland, Deidre Devier
School of Medicine Faculty Publications
Background: Parkinson’s Disease (PD) can include physical signs and possibly cognitive impairment, resulting from the convergence of pathologicalprocesses involving dopaminergic dysfunction, accumulation ofalpha-synuclein, cholinergic deficits, and disruption of otherneurotransmitter systems. We used screening tests to evaluate thecharacteristics of cognitive performance in patients with PD and to assess their validity compared tothe Montreal Cognitive Assessment (MoCA). Methods: This is a natural history study of participants with PD and controls screened for possible cognitive impairment using the MoCA, Symbol Digit Modalities Test (SDMT), and King-Devick (KD). The groups were compared on performance and then factors associated with cognitive performance (age, diagnosis, and …
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
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 …
Upregulating Ankhd1 In Ps19 Mice Reduces Tau Phosphorylation And Mitigates Tau Toxicity-Induced Cognitive Deficits, Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm, Chunlai Wu
Upregulating Ankhd1 In Ps19 Mice Reduces Tau Phosphorylation And Mitigates Tau Toxicity-Induced Cognitive Deficits, Xiaolin Tian, Nathan Le, Yuhai Zhao, Dina Alawamleh, Andrew Schwartz, Lauren Meyer, Elizabeth Helm, Chunlai Wu
School of Graduate Studies Faculty Publications
Using the fly eye as a model system, we previously demonstrated that upregulation of the fly gene mask protects against FUS- and Tau-induced photoreceptor degeneration. Building upon this finding, we investigated whether the protective role of mask is conserved in mammals. To this end, we generated a transgenic mouse line carrying Cre-inducible ANKHD1, the human homolog of mask. Utilizing the TauP301S-PS19 mouse model for Tau-related dementia, we found that expressing ANKHD1 driven by CamK2a-Cre reduced hyperphosphorylated human Tau in 6-month-old mice. Additionally, ANKHD1 expression was associated with a trend toward reduced gliosis and preservation of the presynaptic marker Synaptophysin, suggesting …
Diabetes Mellitus And Associated Vascular Disease: Pathogenesis, Complications, And Evolving Treatments, Kazi Islam, Rahib Islam, Ivan Nguyen, Hassan Malik, Humza Pirzadah, Barsha Shrestha, Isabella B. Lentz, Sahar Shekoohi, Alan D. Kaye
Diabetes Mellitus And Associated Vascular Disease: Pathogenesis, Complications, And Evolving Treatments, Kazi Islam, Rahib Islam, Ivan Nguyen, Hassan Malik, Humza Pirzadah, Barsha Shrestha, Isabella B. Lentz, Sahar Shekoohi, Alan D. Kaye
School of Medicine Faculty Publications
Diabetes mellitus is a metabolic disorder, characterized by elevated blood sugar levels (hyperglycemia) and insulin dysregulation. This disease is associated with morbidity and mortality, including significant potential vascular complications. High levels of hyperglycemia lead to not only elevated levels of reactive oxygen species but also advanced glycation end products, which are detrimental to the vascular endothelium and reduce protective compounds such as nitric oxide and prostacyclin. This damage contributes to the development of both macrovascular and microvascular complications. The present investigation explores the pathophysiological mechanisms of diabetic vascular complications and evaluates current management strategies, including lifestyle modifications, pharmacological treatments, and …
Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou
Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou
School of Medicine Faculty Publications
Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …
The Relationship Between Spectral Signals And Retinal Sensitivity In Dendrobatid Frogs, Whitney G. Walkowski, Corinne L. Richards-Zawacki, William C. Gordon, Nicolas G. Bazan, Hamilton E. Farris
The Relationship Between Spectral Signals And Retinal Sensitivity In Dendrobatid Frogs, Whitney G. Walkowski, Corinne L. Richards-Zawacki, William C. Gordon, Nicolas G. Bazan, Hamilton E. Farris
School of Graduate Studies Faculty Publications
Research on visually driven behavior in anurans has often focused on Dendrobatoidea, a clade with extensive variation in skin reflectance, which is perceived to range from cryptic to conspicuous coloration. Because these skin patterns are important in intraspecific and interspecific communication, we hypothesized that the visual spectral sensitivity of dendrobatids should vary with conspecific skin spectrum. We predicted that the physiological response of frog retinas would be tuned to portions of the visible light spectrum that match their body reflectance. Using wavelength-specific electroretinograms (ERGs; from 350-650 nm), spectrometer measurements, and color-calibrated photography of the skin, we compared retinal sensitivity and …
Riluzole Attenuates Acute Neural Injury And Reactive Gliosis, Hippocampal-Dependent Cognitive Impairments And Spontaneous Recurrent Generalized Seizures In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Dominic Allocco, Laine Vande Hei, Heike Wulff, Jeffrey D. Erickson
Riluzole Attenuates Acute Neural Injury And Reactive Gliosis, Hippocampal-Dependent Cognitive Impairments And Spontaneous Recurrent Generalized Seizures In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Dominic Allocco, Laine Vande Hei, Heike Wulff, Jeffrey D. Erickson
School of Medicine Faculty Publications
Background: Riluzole exhibits neuroprotective and therapeutic effects in several neurological disease models associated with excessive synaptic glutamate (Glu) release. We recently showed riluzole prevents acute excitotoxic hippocampal neural injury at 3 days in the kainic acid (KA) model of temporal lobe epilepsy (TLE). Currently, it is unknown if preventing acute neural injury and the neuroinflammatory response is sufficient to suppress epileptogenesis. Methods: The KA rat model of TLE was used to determine if riluzole attenuates acute hippocampal neural injury and reactive gliosis. KA was administered to adult male Sprague-Dawley (250 g) rats at 5 mg/kg/hr until status epilepticus (SE) was …
A Novel Model Of Autologous Tooth Transplantation For The Study Of Nerve Recruitment, Teresa E. Fowler, Doan T. Bloomquist, Caroline Glessner, Poonam Patel, Jeffrey N. James, Kathryn Bollinger, Lynnette P. Mccluskey, Ryan F. Bloomquist
A Novel Model Of Autologous Tooth Transplantation For The Study Of Nerve Recruitment, Teresa E. Fowler, Doan T. Bloomquist, Caroline Glessner, Poonam Patel, Jeffrey N. James, Kathryn Bollinger, Lynnette P. Mccluskey, Ryan F. Bloomquist
School of Dentistry Faculty Publications
Background: Limited treatment options exist for damaged nerves and despite impressive advances in tissue engineering, scientists and clinicians have yet to fully replicate nerve development and recruitment. Innervation is a critical feature for normal organ function. While most organs are innervated prior to birth, a rare example of postnatal nerve recruitment occurs in the natural development of secondary teeth during adolescence. Many animals undergo postnatal shedding of deciduous teeth with development and eruption of secondary teeth, a process requiring recruitment of nerve and vasculature to each tooth pulp for viability. Here, the investigators created a novel model for the study …
Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator And Microvascular Fragments Promotes The Healing Of Deep Burn Wounds, Yan Lu, Shanchun Su, Chih Chang Chu, Yuichi Kobayashi, Abdul Razak Masoud, Hongying Peng, Nathan Lien, Mingyu He, Christopher Vuong, Ryan Tran, Song Hong
Amino Acid-Based Protein-Mimic Hydrogel Incorporating Pro-Regenerative Lipid Mediator And Microvascular Fragments Promotes The Healing Of Deep Burn Wounds, Yan Lu, Shanchun Su, Chih Chang Chu, Yuichi Kobayashi, Abdul Razak Masoud, Hongying Peng, Nathan Lien, Mingyu He, Christopher Vuong, Ryan Tran, Song Hong
School of Medicine Faculty Publications
Pro-regenerative lipid mediator 1 (PreM1) is a specialized pro-resolving lipid mediator that promotes wound healing and regenerative functions of mesenchymal stem cells (MSCs), endothelial cells, and macrophages. The healing of third-degree (3°) burns and regenerative functions of MSCs are enhanced by ACgel1, an arginine-and-chitosan-based protein-mimic hybrid hydrogel. Adipose-tissue derived microvascular fragments (MVFs) are native vascularization units and a rich source of MSCs, endothelial cells, and perivascular cells for tissue regeneration. Here we describe an innovative PreM1-MVFs-ACgel1 construct that incorporated PreM1 and MVFs into ACgel1 via optimal design and fabrication. This construct delivered PreM1 to 3°-burn wounds at least up to …
The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi
The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi
School of Medicine Faculty Publications
Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such …
Persistent Interruption In Parvalbuminpositive Inhibitory Interneurons: Biophysical And Mathematical Mechanisms, Carol M. Upchurch, Christopher J. Knowlton, Simon Chamberland, Carmen C. Canavier
Persistent Interruption In Parvalbuminpositive Inhibitory Interneurons: Biophysical And Mathematical Mechanisms, Carol M. Upchurch, Christopher J. Knowlton, Simon Chamberland, Carmen C. Canavier
School of Graduate Studies Faculty Publications
Persistent activity in excitatory pyramidal cells (PYRs) is a putative mechanism for maintaining memory traces during working memory. We have recently demonstrated persistent interruption of firing in fastspiking parvalbumin-expressing interneurons (PV-INs), a phenomenon that could serve as a substrate for persistent activity in PYRs through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modeling and mathematical analysis showed that the slowly inactivating potassium current KV1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption …
Riluzole For Degenerative Cervical Myelopathy: A Secondary Analysis Of The Csm-Protect Trial, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Jetan H. Badhiwala, Henry Ahn, H. Francis Farhadi, Christopher I. Shaffrey, Ahmad Nassr, Praveen Mummaneni, Paul M. Arnold, Bradley Jacobs, K. Daniel Riew, Michael Kelly, Darrel S. Brodke, Alexander R. Vaccaro, Alan S. Hilibrand, Jason Wilson, James S. Harrop, S. Timm Yoon, Kee D. Kim, Daryl R. Fourney, Carlo Santaguida, Eric M. Massicotte, Peng Huang
Riluzole For Degenerative Cervical Myelopathy: A Secondary Analysis Of The Csm-Protect Trial, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Jetan H. Badhiwala, Henry Ahn, H. Francis Farhadi, Christopher I. Shaffrey, Ahmad Nassr, Praveen Mummaneni, Paul M. Arnold, Bradley Jacobs, K. Daniel Riew, Michael Kelly, Darrel S. Brodke, Alexander R. Vaccaro, Alan S. Hilibrand, Jason Wilson, James S. Harrop, S. Timm Yoon, Kee D. Kim, Daryl R. Fourney, Carlo Santaguida, Eric M. Massicotte, Peng Huang
School of Medicine Faculty Publications
Importance: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical …
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
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 …
Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff
Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff
School of Dentistry Faculty Publications
Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. …
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
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 …
Novel Lipid Mediator 7s,14r-Docosahexaenoic Acid: Biogenesis And Harnessing Mesenchymal Stem Cells To Ameliorate Diabetic Mellitus And Retinal Pericyte Loss, Yan Lu, Haibin Tian, Hongying Peng, Quansheng Wang, Bruce A. Bunnell, Nicolas G. Bazan, Song Hong
Novel Lipid Mediator 7s,14r-Docosahexaenoic Acid: Biogenesis And Harnessing Mesenchymal Stem Cells To Ameliorate Diabetic Mellitus And Retinal Pericyte Loss, Yan Lu, Haibin Tian, Hongying Peng, Quansheng Wang, Bruce A. Bunnell, Nicolas G. Bazan, Song Hong
School of Medicine Faculty Publications
Introduction: Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. Methods: MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Results: Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by …
Synchrony In Networks Of Type 2 Interneurons Is More Robust To Noise With Hyperpolarizing Inhibition Compared To Shunting Inhibition In Both The Stochastic Population Oscillator And The Coupled Oscillator Regimes, Roman Baravalle, Carmen C. Canavier
Synchrony In Networks Of Type 2 Interneurons Is More Robust To Noise With Hyperpolarizing Inhibition Compared To Shunting Inhibition In Both The Stochastic Population Oscillator And The Coupled Oscillator Regimes, Roman Baravalle, Carmen C. Canavier
School of Medicine Faculty Publications
Synchronization in the gamma band (25–150 Hz) is mediated by PV+ inhibitory interneurons, and evidence is accumulating for the essential role of gamma oscillations in cognition. Oscillations can arise in inhibitory networks via synaptic interactions between individual oscillatory neurons (mean-driven) or via strong recurrent inhibition that destabilizes the stationary background firing rate in the fluctuation-driven balanced state, causing an oscillation in the population firing rate. Previous theoretical work focused on model neurons with Hodgkin’s Type 1 excitability (integrators) connected by current-based synapses. Here we show that networks comprised of simple Type 2 oscillators (resonators) exhibit a supercritical Hopf bifurcation between …
Bactericidal Efficacy Of The Combination Of Maresin-Like Proresolving Mediators And Carbenicillin Action On Biofilm-Forming Burn Trauma Infection-Related Bacteria, Anbu Mozhi Thamizhchelvan, Abdul Razak Masoud, Shanchun Su, Yan Lu, Hongying Peng, Yuichi Kobayashi, Yu Wang, Nathan K. Archer, Song Hong
Bactericidal Efficacy Of The Combination Of Maresin-Like Proresolving Mediators And Carbenicillin Action On Biofilm-Forming Burn Trauma Infection-Related Bacteria, Anbu Mozhi Thamizhchelvan, Abdul Razak Masoud, Shanchun Su, Yan Lu, Hongying Peng, Yuichi Kobayashi, Yu Wang, Nathan K. Archer, Song Hong
School of Medicine Faculty Publications
Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading …
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
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 …
Development Of A Novel Covalently Bonded Conjugate Of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) For Wound-Compatible And Injectable Hydrogel To Accelerate Healing, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Jibao He, Song Hong
Development Of A Novel Covalently Bonded Conjugate Of Caprylic Acid Tripeptide (Isoleucine–Leucine–Aspartic Acid) For Wound-Compatible And Injectable Hydrogel To Accelerate Healing, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Jibao He, Song Hong
School of Medicine Faculty Publications
Third-degree burn injuries pose a significant health threat. Safer, easier-to-use, and more effective techniques are urgently needed for their treatment. We hypothesized that covalently bonded conjugates of fatty acids and tripeptides can form wound-compatible hydrogels that can accelerate healing. We first designed conjugated structures as fatty acid–aminoacid1–amonoacid2–aspartate amphiphiles (Cn acid–AA1–AA2–D), which were potentially capable of self-assembling into hydrogels according to the structure and properties of each moiety. We then generated 14 novel conjugates based on this design by using two Fmoc/tBu solid-phase peptide synthesis techniques; we verified their structures and purities through liquid chromatography with tandem mass spectrometry and nuclear …
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …
Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw
Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw
School of Medicine Faculty Publications
AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …
Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson
Riluzole And Novel Naphthalenyl Substituted Aminothiazole Derivatives Prevent Acute Neural Excitotoxic Injury In A Rat Model Of Temporal Lobe Epilepsy, Thomas Kyllo, Vikrant Singh, Heesung Shim, Singh Latika, Hai M. Nguyen, Yi Je Chen, Ellen Terry, Heike Wulff, Jeffrey D. Erickson
School of Medicine Faculty Publications
Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When …
Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue
Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue
School of Medicine Faculty Publications
The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …
Cancer As A Channelopathy—Appreciation Of Complimentary Pathways Provides A Different Perspective For Developing Treatments, Harry J. [email protected] Gould, Dennis Paul
Cancer As A Channelopathy—Appreciation Of Complimentary Pathways Provides A Different Perspective For Developing Treatments, Harry J. [email protected] Gould, Dennis Paul
School of Medicine Faculty Publications
Life depends upon the ability of cells to evaluate and adapt to a constantly changing environment and to maintain internal stability to allow essential biochemical reactions to occur. Ions and ion channels play a crucial role in this process and are essential for survival. Alterations in the expression of the transmembrane proteins responsible for maintaining ion balance that occur as a result of mutations in the genetic code or in response to iatrogenically induced changes in the extracellular environment is a characteristic feature of oncogenesis and identifies cancer as one of a constellation of diseases known as channelopathies. The classification …
Synergistic Neuroprotection By A Paf Antagonist Plus A Docosanoid In Experimental Ischemic Stroke: Dose-Response And Therapeutic Window, Madigan M. Reid, Andre Obenaus, Pranab K. Mukherjee, Larissa Khoutorova, Cassia R. Roque, Nicos A. Petasis, Reinaldo B. Oria, Ludmila Belayev, Nicolas G. Bazan
Synergistic Neuroprotection By A Paf Antagonist Plus A Docosanoid In Experimental Ischemic Stroke: Dose-Response And Therapeutic Window, Madigan M. Reid, Andre Obenaus, Pranab K. Mukherjee, Larissa Khoutorova, Cassia R. Roque, Nicos A. Petasis, Reinaldo B. Oria, Ludmila Belayev, Nicolas G. Bazan
School of Graduate Studies Faculty Publications
Objective: We tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated. Materials and methods: Male SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or …
Biallelic Variants In Wars1 Cause A Highly Variable Neurodevelopmental Syndrome And Implicate A Critical Exon For Normal Auditory Function, Sheng Jia Lin, Barbara Vona, Hillary M. Porter, Mahmoud Izadi, Kevin Huang, Yves Lacassie, Jill A. Rosenfeld, Saadullah Khan, Cassidy Petree, Tayyiba A. Ali, Nazif Muhammad, Sher A. Khan, Noor Muhammad, Pengfei Liu, Marie Louise Haymon, Franz Rüschendorf, Il Keun Kong, Linda Schnapp, Natasha Shur, Lynn Chorich, Lawrence Layman, Thomas Haaf, Ehsan Pourkarimi, Hyung Goo Kim, Gaurav K. Varshney
Biallelic Variants In Wars1 Cause A Highly Variable Neurodevelopmental Syndrome And Implicate A Critical Exon For Normal Auditory Function, Sheng Jia Lin, Barbara Vona, Hillary M. Porter, Mahmoud Izadi, Kevin Huang, Yves Lacassie, Jill A. Rosenfeld, Saadullah Khan, Cassidy Petree, Tayyiba A. Ali, Nazif Muhammad, Sher A. Khan, Noor Muhammad, Pengfei Liu, Marie Louise Haymon, Franz Rüschendorf, Il Keun Kong, Linda Schnapp, Natasha Shur, Lynn Chorich, Lawrence Layman, Thomas Haaf, Ehsan Pourkarimi, Hyung Goo Kim, Gaurav K. Varshney
School of Medicine Faculty Publications
Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well …
Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan
Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan
School of Medicine Faculty Publications
Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …