Article
Biochemistry & Molecular Biology
Maria Florencia Acutain, Maria Veronica Baez
Summary: NMDA receptors play a vital role in synaptic plasticity. GluN2A and GluN2B are the most common NMDA receptor regulatory subunits, and changes in GluN2A expression are associated with complex neurodevelopmental disorders. Decreasing GluN2A expression in mature neurons leads to an immature phenotype with enhanced response to glutamate stimulus.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Neurosciences
Yang Ge, Yu Tian Wang
Summary: Glutamate N-methyl-D-aspartate receptor (NMDAR) containing GluN2B subunit is crucial for synaptic plasticity and neuronal viability. GluN2B-containing NMDARs can exist as diheteromeric and triheteromeric receptors in mature neurons, and their C-terminal region forms complexes with intracellular signaling proteins, important for synaptic plasticity and neuronal survival. Dysregulation of GluN2B-containing NMDARs and their downstream signaling pathways is implicated in neurological diseases, and strategies to reverse these deficits have been investigated. This article provides an overview of GluN2B-containing NMDAR pharmacology and its physiological functions, emphasizing its importance in both health and disease.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Abdallah Ahnaou, Kobe Heleven, Ria Biermans, Nikolay Manyakov, Wilhelmus H. Drinkenburg
Summary: This study highlights the importance of NMDAR in LTP synaptic plasticity, but specific blockade of the NR2B subunit does not alter hippocampal LTP. Pharmacokinetics at the doses used may have contributed to the lack of effects with specific antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Jacob A. Bahry, Karlie N. Fedder-Semmes, Michael P. Sceniak, Shasta L. Sabo
Summary: Mutations in the GRIN2B gene lead to autism spectrum disorders, with a GluN2B variant affecting dendrite morphogenesis by shifting branch growth towards retraction. Mutant neurons exhibit increased pruning of dendritic branches despite forming new branches at similar rates to wild-type neurons. This results in a nearly complete elimination of the net expansion of arbor size and complexity during developmental periods.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Can Ozden, Roman Sloutsky, Tomohiro Mitsugi, Nicholas Santos, Emily Agnello, Christl Gaubitz, Joshua Foster, Emily Lapinskas, Edward A. Esposito, Takeo Saneyoshi, Brian A. Kelch, Scott C. Garman, Yasunori Hayashi, Margaret M. Stratton
Summary: This study investigates the activation mechanism of CaMKII using X-ray crystallography, molecular dynamics simulations, and biochemistry. The results show that contrary to the previously believed two distinct sites, activators and substrates actually bind to a single continuous site on the kinase domain. Through kinetic competition with the regulatory segment, high-affinity binding partners sustain the activity of CaMKII, allowing substrate phosphorylation.
Article
Cell Biology
Jolie Barter, Ashok Kumar, Linda Bean, Marissa Ciesla, Thomas C. Foster
Summary: Long-term systemic inflammation can lead to memory impairment in aged animals, while having a lesser impact on younger animals. After 12 months post-injections, changes in gene expression related to synaptic transmission and regulation of inflammatory signals were observed.
Review
Biochemistry & Molecular Biology
Guendalina Olivero, Alessandra Roggeri, Anna Pittaluga
Summary: Autoantibodies against NMDA and AMPA receptors in the central nervous system can lead to neurological and psychiatric symptoms and disrupt synaptic communication. Understanding the molecular mechanisms involved in these autoantibody-mediated effects is crucial for understanding their pathogenic role in central disorders and developing new therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Arne W. Mould, Noura Al-Juffali, Annette von Delft, Paul E. Brennan, Elizabeth M. Tunbridge
Summary: The study examines the role of kalirin in brain function and its therapeutic potential in schizophrenia, focusing on its regulation of synapse formation and stabilization. The need for further understanding of the diversity and function of its isoforms is highlighted, along with their changes across neurodevelopment and effects on brain function in vivo.
Review
Neurosciences
Jesse E. Hanson, Hongjie Yuan, Riley E. Perszyk, Tue G. Banke, Hao Xing, Ming-Chi Tsai, Frank S. Menniti, Stephen F. Traynelis
Summary: N-methyl-D-aspartate (NMDA) receptors play a role in excitatory synaptic transmission, are present throughout the central nervous system, and are involved in synaptic plasticity. NMDA receptor modulators have shown potential in treating psychiatric disorders, neurodevelopmental disorders, and neurodegenerative conditions. Recent research has discovered that certain NMDA receptor inhibitors can rapidly and significantly alleviate depression by inducing long-lasting changes in the brain. This has led to new studies exploring the therapeutic applications of NMDA receptor antagonists. Positive allosteric modulators of NMDA receptors are also being investigated for enhancing synaptic function in diseases with NMDA receptor dysfunction. However, the use of NMDA receptor modulators comes with potential risks. Therefore, further research is needed to fully understand and harness the therapeutic potential of targeting this important receptor class.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
ChangHui Pak, Tamas Danko, Vincent R. Mirabella, Jinzhao Wang, Yingfei Liu, Madhuri Vangipuram, Sarah Grieder, Xianglong Zhang, Thomas Ward, Yu-Wen Alvin Huang, Kang Jin, Philip Dexheimer, Eric Bardes, Alexis Mitelpunkt, Junyi Ma, Michael McLachlan, Jennifer C. Moore, Pingping Qu, Carolin Purmann, Jeffrey L. Dage, Bradley J. Swanson, Alexander E. Urban, Bruce J. Aronow, Zhiping P. Pang, Douglas F. Levinson, Marius Wernig, Thomas C. Sudhof
Summary: Heterozygous NRXN1 deletions are associated with schizophrenia and other neurodevelopmental disorders, causing impaired neurotransmitter release in human neurons. However, mouse neurons with NRXN1 deletions did not show the same impairment, suggesting a human-specific phenotype. The deletions also led to increased levels of CASK and characteristic gene-expression changes, highlighting the potential for future drug discovery targeting NRXN1 deletions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Sam A. Booker, David J. A. Wyllie
Summary: NMDARs are essential for synaptic information transfer and plasticity in the majority of brain circuits. Inhibitory GABAergic interneurons exhibit diverse NMDAR expression and function, controlling cellular excitation in a synapse-specific manner. Further research is needed to fully understand the role of NMDARs in modulating GABAergic synaptic and circuit function.
Article
Cell Biology
Yanke Zhang, Junhong Wu, Yin Yan, Yixue Gu, Yuanlin Ma, Min Wang, Hui Zhang, Kaiyan Tao, Yang Lu, Weihua Yu, Wei Jing, Xuefeng Wang, Xin Tian
Summary: SAPAP3 has been found to play a potential role in epilepsy, as its expression levels were significantly increased in patients with epilepsy and mouse models of epilepsy. Decreasing SAPAP3 levels can alleviate seizure severity, while overexpression of SAPAP3 has the opposite effect. Furthermore, SAPAP3 affects neuronal action potentials, miniature excitatory postsynaptic currents, and NMDAR-mediated currents, indicating its important role in excitatory synaptic transmission.
CELL DEATH & DISEASE
(2022)
Article
Neurosciences
S. Murat Durakoglugil, R. Catherine Wasser, H. Connie Wong, Theresa Pohlkamp, Xunde Xian, Courtney Lane-Donovan, Katja Fritschle, Lea Naestle, Joachim Herz
Summary: Alzheimer's disease is characterized by the accumulation of Aβ plaques and neurofibrillary tangles, leading to synaptic dysfunction. Reelin protects synapses against Aβ toxicity through ApoE receptors. Experiments showed that Reelin modulates mGluR-LTD, potentially impacting memory consolidation or neurodegeneration.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Beata Dabrowska-Bouta, Grzegorz Sulkowski, Mikolaj Salek, Malgorzata Frontczak-Baniewicz, Lidia Struzynska
Summary: Silver nanoparticles have strong antimicrobial properties, but also exhibit neurotoxicity by affecting the NMDA receptor complex and signaling pathways in immature rats, potentially leading to health hazards in children and infants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kayla Farrell, Madeline Musaus, Aubrey Auerbach, Shaghayegh Navabpour, W. Keith Ray, Richard F. Helm, Timothy J. Jarome
Summary: Females have higher levels of proteasome-independent K63-polyubiquitination in the amygdala following fear conditioning, which is involved in regulating ATP synthesis and proteasome activity. Knockdown of K63-polyubiquitination impairs fear memory and reduces ATP levels and proteasome activity in female rats, but not in males. These findings provide the first evidence linking proteasome-independent and proteasome-dependent UPS functions in fear memory formation and may contribute to understanding the sex differences in PTSD development.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Rebecca S. Hofford, Scott J. Russo, Drew D. Kiraly
EUROPEAN JOURNAL OF NEUROSCIENCE
(2019)
Article
Biochemistry & Molecular Biology
Fouad Lemtiri-Chlieh, Stefan T. Arold, Chris Gehring
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Substance Abuse
Richard Lieberman, Kevin P. Jensen, Kaitlin Clinton, Eric S. Levine, Henry R. Kranzler, Jonathan Covault
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Carissa L. Sirois, Judy E. Bloom, James J. Fink, Dea Gorka, Steffen Keller, Noelle D. Germain, Eric S. Levine, Stormy J. Chamberlain
HUMAN MOLECULAR GENETICS
(2020)
Article
Neurosciences
Rebecca S. Hofford, Tanner J. Euston, Rashaun S. Wilson, Katherine R. Meckel, Emily G. Peck, Arthur Godino, Joseph A. Landry, Erin S. Calipari, TuKiet T. Lam, Drew D. Kiraly
Summary: The research shows that G-CSF can accelerate cocaine extinction and reduce cue-induced cocaine seeking during abstinence by regulating proteins related to synapse and glutamate signaling in the mPFC. These findings suggest that G-CSF may serve as a research target to reduce drug craving or seeking behaviors, and its FDA-approved status could facilitate clinical translation swiftly.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Plant Sciences
Mashael Alqahtani, Damien J. Lightfoot, Fouad Lemtiri-Chlieh, Ebtihaj Bukhari, Jose M. Pardo, Magdalena M. Julkowska, Mark Tester
Summary: This study investigated the role of PQL proteins in mediating sodium influx in plant roots and their potential contribution to salt tolerance. Results showed that expression of AtPQL1a, AtPQL1b, and AtPQL1c was upregulated under salt stress, affecting root growth and overall development in plants.
Article
Neurosciences
James J. Fink, Jeremy D. Schreiner, Judy E. Bloom, Jadin James, Dylan S. Baker, Tiwanna M. Robinson, Richard Lieberman, Leslie M. Loew, Stormy J. Chamberlain, Eric S. Levine
Summary: The study investigated electrophysiological phenotypes in induced pluripotent stem cell-derived neurons from patients with Dup15q, revealing several potential mechanisms of neuronal hyperexcitability and seizure susceptibility. These findings may offer new targets for the treatment of seizures and other associated phenotypes in Dup15q.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Rebecca S. Hofford, Nicholas L. Mervosh, Tanner J. Euston, Katherine R. Meckel, Amon T. Orr, Drew D. Kiraly
Summary: Recent evidence has shown the significant impact of the gut microbiome on neuronal function and behavior, with disruptions linked to various neuropsychiatric disorders. While the role of the microbiome in substance use disorders is not fully understood, a study on male mice with depleted gut microbiome showed decreased morphine conditioned place preference and gene expression changes in response to high-dose morphine. Short-chain fatty acids were identified as crucial mediators of gut-brain communication responsible for the effects on morphine reward caused by microbiome depletion.
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Lillian J. Brady, Kirsty R. Erickson, Kelsey E. Lucerne, Aya Osman, Drew D. Kiraly, Erin S. Calipari
Summary: Cocaine use disorder is associated with alterations in immune function and changes in peripheral cytokine expression, impacting responses to drug-related cues and highlighting the critical interaction between the brain and immune system. Upregulation of granulocyte colony-stimulating factor (G-CSF) by cocaine enhances the drug's effects on dopamine terminals through a release-based mechanism, indicating a potential role of immune factors in altering drug responses.
PSYCHOPHARMACOLOGY
(2021)
Article
Physiology
Fouad Lemtiri-Chlieh, Dylan S. Baker, Iman M. Al-Naggar, Ramalakshmi Ramasamy, George A. Kuchel, Eric S. Levine, Paul Robson, Phillip P. Smith
Summary: This study reveals the mechanism of action of hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels in bladder control. The authors found that HCN is predominantly expressed in a subpopulation of detrusor smooth myocytes in mice, and its activation reduces sustained detrusor tension through cAMP signaling, without affecting intermittent detrusor activity.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2022)
Article
Neurosciences
Fouad Lemtiri-Chlieh, Eric S. Levine
Summary: It is widely accepted that exogenous cannabinoids can impair short-term memory and cognition. Conversely, the activation of endogenous cannabinoids may enhance synaptic plasticity. This study found that the simultaneous activation of CB1 receptors by 2-AG and anandamide enhances LTP by suppressing inhibition at GABAergic synapses.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Marwa Elamin, Fouad Lemtiri-Chlieh, Tiwanna M. Robinson, Eric S. Levine
Summary: This study investigates the sodium channel kinetics in Dup15q neurons, a neurodevelopmental disorder associated with autism and seizures. The Dup15q neurons showed increased sodium current density, depolarizing shift in steady-state inactivation, delayed onset of slow inactivation, and faster recovery from inactivation processes. These dysfunctional inactivation kinetics may contribute to the development of seizures in Dup15q patients and suggest the potential use of drugs that modulate inactivation kinetics for therapeutic approaches.
Article
Cell & Tissue Engineering
Marwa Elamin, Aurelie Dumarchey, Christopher Stoddard, Tiwanna M. Robinson, Christopher Cowie, Dea Gorka, Stormy J. Chamberlain, Eric S. Levine
Summary: Chromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder characterized by autism and epilepsy. UBE3A, an imprinted gene expressed only from the maternal allele, is believed to be a major driver of Dup15q. In this study, Dup15q neurons showed increased excitability compared to control neurons, and normalizing UBE3A levels using antisense oligonucleotides prevented this phenotype. However, UBE3A overexpression resulted in a similar profile to Dup15q neurons, suggesting the involvement of other genes in the duplicated region.
Article
Neurosciences
Katherine R. Meckel, Sierra S. Simpson, Arthur Godino, Emily G. Peck, Jonathon P. Sens, Michael Z. Leonard, Olivier George, Erin S. Calipari, Rebecca S. Hofford, Drew D. Kiraly
Summary: Cocaine use disorder is a public health crisis and there are currently no FDA-approved medications for its treatment. Research has shown the important role of the gut microbiome and its metabolites in modulating drug-seeking behaviors, but their impact on relapse after prolonged abstinence is unknown. This study reveals that depletion of the gut microbiome enhances cocaine-seeking behavior, while restoration of bacterially-derived metabolites reverses this effect, suggesting the potential of the microbiome as a target for translational research.
NEUROPSYCHOPHARMACOLOGY
(2023)
Meeting Abstract
Substance Abuse
R. S. Hofford, K. R. Meckel, D. D. Kiraly
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2019)