Article
Multidisciplinary Sciences
Jennifer L. Peotter, Iryna Pustova, Molly M. Lettman, Shalini Shatadal, Mazdak M. Bradberry, Allison D. Winter-Reed, Maya Charan, Erin E. Sharkey, James R. Alvin, Alyssa M. Bren, Annika K. Oie, Edwin R. Chapman, M. Shahriar Salamat, Anjon Audhya
Summary: We demonstrate that the TFG p.R106C variant is associated with progressive spastic paraparesis, ventriculomegaly, and thinning of the corpus callosum. We find that TFG plays a role in the transport of secretory proteins from the ER and the trafficking of Rab4A-positive recycling endosomes in axons and dendrites. Impaired TFG function leads to down-regulated inhibitory receptor signaling and may contribute to imbalances in excitation-inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Maria Italia, Elena Ferrari, Monica Di Luca, Fabrizio Gardoni
Summary: AMPARs play a crucial role in excitatory synaptic transmission in the mammalian brain, with the GluA3 subunit being widely expressed and functionally relevant. Modulation of GluA3 through pharmacological means may offer a new approach for addressing altered glutamatergic synapses associated with neurodegenerative and neurodevelopmental disorders.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Irene Martinez-Gallego, Antonio Rodriguez-Moreno, Yuniesky Andrade-Talavera
Summary: In this article, the involvement of group I mGluRs in STDP and their possible role as coincidence detectors are briefly reviewed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Anna Bodzeta, Nicky Scheefhals, Harold D. MacGillavry
Summary: The various functions of glutamate in the brain are mediated by ionotropic and metabotropic glutamate receptors, which modulate synaptic transmission and plasticity. mGluRs play roles at both presynaptic and postsynaptic sites, acting as essential signal integrators that couple mechanisms of transmission and plasticity.
Editorial Material
Biochemistry & Molecular Biology
Colin Brownlee
Summary: A new study has identified the major components that enable the Venus flytrap to fire action potentials, revealing the recruitment of different ion channels and transporters that give rise to this unique plant behavioral response.
Review
Neurosciences
Jeremy M. Henley, Jithin D. Nair, Richard Seager, Busra P. Yucel, Gavin Woodhall, Benjamin S. Henley, Karolina Talandyte, Hope I. Needs, Kevin A. Wilkinson
Summary: Epilepsy is caused by abnormal neuronal network activity. The review focuses on the role and regulation of kainate and AMPA receptors in seizure activity, discussing the impact of GluK2 and GluA2 subunits on their respective receptors' properties.
Article
Biochemistry & Molecular Biology
Hongxia Xiu, Yajie Liu, Huihui Yang, Haibin Ren, Bowen Luo, Zhipeng Wang, Hong Shao, Fengzhong Wang, Jingjian Zhang, Yutang Wang
Summary: This study proposes an in silico method to identify novel umami-tasting molecules using QSAR models, PCA, molecular docking, and electronic tongue analysis. A total of 169 potential umami molecules were identified, with 18 molecules confirmed as umami molecules through electronic tongue analysis. This work holds promise in elucidating the crystal structure of umami receptors and taste-sensing mechanisms, as well as the practical application of new umami molecules in food.
Article
Neurosciences
Marharyta Kolcheva, Marek Ladislav, Jakub Netolicky, Stepan Kortus, Kristyna Rehakova, Barbora Hrcka Krausova, Katarina Hemelikova, Anna Misiachna, Anna Kadkova, Martin Klima, Dominika Chalupska, Martin Horak
Summary: N-methyl-D-aspartate receptors (NMDARs) play essential roles in neurotransmission and have been associated with developmental delay and seizures. This study characterizes the functional and pharmacological effects of a pathogenic variant in the GluN1 subunit, providing important insights into its impact on receptor expression and potency.
Review
Neurosciences
Jonathan G. Hanley
Summary: AMPA receptors play a critical role in synaptic transmission and brain function, with their expression at synapses determining functional connectivity of neuronal circuits and underpinning learning and memory. Dysregulation of excitatory synaptic transmission and plasticity processes is involved in various neurological disorders. MiRNAs play a role in regulating AMPAR subunit expression and synaptic plasticity, potentially contributing to both physiological and pathological changes in the brain.
Article
Multidisciplinary Sciences
Paola Muttathukunnel, Patrick Frei, Sarah Perry, Dion Dickman, Martin Mueller
Summary: Robust neural information transfer relies on the delicate molecular nano-architecture of chemical synapses. This study reveals the alignment of presynaptic nanorings with postsynaptic glutamate receptor rings and the formation of nanocolumn rings by presynaptic proteins and glutamate receptors. The impairment of glutamate receptors triggers the formation of transsynaptic nanocolumns on a minute timescale during homeostatic plasticity. This research uncovers the regulatory mechanism of synaptic nano-architecture and highlights its importance in stabilizing synaptic transmission.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Hanke Gwendolyn Bauersachs, Ursula Weiss, Andrea Hellwig, Celia Garcia-Vilela, Bastienne Zaremba, Henrik Kaessmann, Priit Pruunsild, Hilmar Bading
Summary: Studies in rodent models have shown that glutamate-induced excitotoxic cell death is primarily mediated by extrasynaptic NMDARs. Rodent neurons can develop a protective shield against excitotoxicity in an activity-dependent manner. This study established a human iPSC-derived forebrain organoid model and found that both toxic and protective actions of NMDARs are preserved in human neurons. The experimental platform described here is valuable for validating neuroprotective gene products and drugs in human neurons.
Article
Engineering, Environmental
Bo Wang, Ting Zhao, Xiao-Xi Chen, Yan-Yan Zhu, Xue Lu, Qing-Hua Qian, Hui-Ru Chen, Xiu-Hong Meng, Hua Wang, Wei Wei, De-Xiang Xu
Summary: The study found that gestational exposure to 1-NP caused anxiety-like behavior in male adult offspring and impaired dendritic arborization, dendritic length, and dendritic spine density in the ventral hippocampus. Gephyrin-related genes, Nrg1 and Erbb4, were also decreased in 1-NP-exposed fetuses, along with decreased TET activity and α-KG content in the fetal forebrain. Supplementation with α-KG ameliorated the effects of 1-NP, improving synaptic plasticity and anxiety-like behavior in male adult offspring.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Cell Biology
Joshua D. Garcia, Sara E. Gookin, Kevin C. Crosby, Samantha L. Schwartz, Erika Tiemeier, Matthew J. Kennedy, Mark L. Dell'Acqua, Paco S. Herson, Nidia Quillinan, Katharine R. Smith
Summary: Inhibitory synapses are dismantled in a sequential manner following excitotoxicity, with GABA(A)R and gephyrin playing crucial roles. The disassembly process is regulated by calcineurin and calpain, and preserving inhibitory synapses may prevent the progression of hyperexcitability.
Article
Behavioral Sciences
Baixia Li, Qian Mao, Na Zhao, Jie Xia, Yongcai Zhao, Bo Xu
Summary: The study investigated the association between exercise-ameliorated Alzheimer's disease with changes in ionic glutamate receptors, showing that 12-week treadmill exercise improved spatial learning and memory abilities of TgAPP/PS1 mice, reduced A beta levels in hippocampus and increased synaptic density and thickness.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Pauline Jeckel, Martin Kriebel, Hansjuergen Volkmer
Summary: The passage explains the connection between autism spectrum disorder and excitatory/inhibitory imbalance in neuronal network connectivity. It discusses how gene mutations, including Met and downstream components, impact synapse formation and stabilization, and highlights Met's role in stabilizing GABAergic synapses through gephyrin clustering.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Plant Sciences
Manuel Candelario, Erika Cuellar, Jorge Mauricio Reyes-Ruiz, Narek Darabedian, Zhou Feimeng, Ricardo Miledi, Amelia Russo-Neustadt, Agenor Limon
JOURNAL OF ETHNOPHARMACOLOGY
(2015)
Review
Behavioral Sciences
Agenor Limon, Firoza Mamdani, Brooke E. Hjelm, Marquis P. Vawter, Adolfo Sequeira
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2016)
Article
Cell Biology
David Baglietto-Vargas, Gilberto Aleph Prieto, Agenor Limon, Stefania Forner, Carlos J. Rodriguez-Ortiz, Kenji Ikemura, Rahasson R. Ager, Rodrigo Medeiros, Laura Trujillo-Estrada, Alessandra C. Martini, Masashi Kitazawa, Jose C. Davila, Carl W. Cotman, Antonia Gutierrez, Frank M. LaFerla
Article
Neurosciences
Agenor Limon, Garo Hagopian, Jorge M. Reyes-Ruiz, Ricardo Miledi
Article
Psychiatry
A. Limon, E. Delbruck, A. Yassine, D. Pandya, R. M. Myers, J. D. Barchas, F. Lee, Schatzberg, S. J. Watson, H. Akil, W. E. Bunney, M. P. Vawter, A. Sequeira
TRANSLATIONAL PSYCHIATRY
(2019)
Article
Multidisciplinary Sciences
Pietro Scaduto, Adolfo Sequeira, Marquis P. Vawter, William Bunney, Agenor Limon
SCIENTIFIC REPORTS
(2020)
Article
Psychiatry
Tommaso Zeppillo, Anton Schulmann, Fabio Macciardi, Brooke E. Hjelm, Melanie Focking, P. Adolfo Sequeira, Ilaria Guella, David Cotter, William E. Bunney, Agenor Limon, Marquis P. Vawter
Summary: Clinical and preclinical studies indicate that synaptic dysfunction of glutamatergic signaling may be related to the behavioral alterations observed in schizophrenia. This study used human postmortem brain synaptic membranes to investigate the impact of gene and protein alterations on the electrophysiological activity of AMPA-type glutamate receptors. The results suggest that transcriptomic and proteomic alterations in the dorsolateral prefrontal cortex of schizophrenia patients contribute to the impaired function of AMPA receptors at the synaptic level.
SCHIZOPHRENIA RESEARCH
(2022)
Article
Multidisciplinary Sciences
Kevin Shen, Tommaso Zeppillo, Agenor Limon
SCIENTIFIC REPORTS
(2020)
Review
Neurosciences
Kevin Shen, Agenor Limon
Summary: AMPA receptors play a crucial role in brain function and their dysregulation is linked to various diseases; studies have focused on the subunits that make up the channel and define AMPARs, but a better understanding of the diversity and regional expression of accessory proteins is needed.
NEUROSCIENCE LETTERS
(2021)
Review
Biochemistry & Molecular Biology
Berenice A. Gutierrez, Agenor Limon
Summary: Neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, result from the dysfunction and death of neurons. The presence of small soluble oligomers, such as amyloid beta and Tau oligomers in Alzheimer's, and alpha-synuclein oligomers in Parkinson's, is toxic and relevant to the development of these diseases. These oligomers increase during the early stages of pathology, leading to disruption of synaptic plasticity, synapse loss, inflammation, imbalance between excitatory and inhibitory transmission, and cognitive impairment. The absence of Tau oligomers at synapses in individuals with advanced Alzheimer's pathology but preserved cognition suggests that resilience mechanisms may depend on the interactions between soluble oligomers and their synaptic targets.
Article
Biochemistry & Molecular Biology
Brice Miller, Naomi Moreno, Berenice A. Gutierrez, Agenor Limon
Summary: Microtransplantation of native synaptosomes provides a better method for studying the electrophysiological properties of mGluRs as it can replicate the characteristics of native receptors. This study confirmed the expression of mGluR1 and mGluR5 in synaptosomes and demonstrated the significant role of mGluR5 in glutamate metabolism signaling.
Article
Psychiatry
Anton Schulmann, Stefano Marenco, Marquis P. Vawter, Nirmala Akula, Agenor Limon, Ajeet Mandal, Pavan K. Auluck, Yash Patel, Barbara K. Lipska, Francis J. McMahon
Summary: Recent postmortem transcriptomic studies have found many differentially expressed genes in schizophrenia, but the relationship between these gene expression changes and antipsychotic drug exposure is uncertain. Comparing gene expression in the prefrontal cortex of schizophrenic patients who were positive or negative for antipsychotic drugs at the time of death, we found that drug exposure had significant effects on the brain transcriptome, especially with atypical antipsychotic drugs. Macaque brain transcriptome data also showed that antipsychotic drugs affect the expression of functionally relevant genes, some of which were also changed in schizophrenia. Co-expression modules related to synaptic function had similar patterns in schizophrenia and antipsychotic drug effects, while modules associated with inflammation and glucose metabolism showed predominantly different patterns. Cell-type shifts in schizophrenia were largely unaffected by antipsychotic drug use. These findings suggest that antipsychotic drugs may confound gene expression changes related to schizophrenia in postmortem brain tissue, and unraveling these effects can help identify causal genes and improve our understanding of the neurobiology of schizophrenia.
TRANSLATIONAL PSYCHIATRY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Agenor Limon, Cesar Mattei
Article
Biology
Adolfo Sequeira, Kevin Shen, Assaf Gottlieb, Agenor Limon
COMMUNICATIONS BIOLOGY
(2019)
Article
Neurosciences
Valeria Lallai, Nickolas Grimes, James P. Fowler, P. Adolfo Sequeira, Preston Cartagena, Agenor Limon, Margaret Coutts, Edwin S. Monuki, William Bunney, Angelo Demuro, Christie D. Fowlers