Article
Biochemistry & Molecular Biology
Ling Chen, Ting Luo, Wenxiu Cui, Manming Zhu, Zucai Xu, Hao Huang
Summary: This study investigates the role and mechanism of Kalirin in epileptogenesis. The results suggest that inhibition of Kalirin can alleviate the severity of seizures, prolong the latent period of the first attack, and modulate the activity of Rac1, providing a novel anti-epileptic target.
JOURNAL OF CHEMICAL NEUROANATOMY
(2023)
Review
Neurosciences
Kevin C. Gonzalez, Attila Losonczy, Adrian Negrean
Summary: In vitro experiments have greatly contributed to our understanding of dendritic and synaptic physiology, but there is a need to translate existing knowledge to in vivo experimental conditions. Changes in ionic composition can alter dendritic excitability and plasticity induction.
Review
Biochemistry & Molecular Biology
Ewa Baczynska, Katarzyna Karolina Pels, Subhadip Basu, Jakub Wlodarczyk, Blazej Ruszczycki
Summary: This article reviews experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. By comparing various methodological pipelines and systematically summarizing the methodology and results of relevant experiments, the focus is on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Biochemistry & Molecular Biology
David Colameo, Gerhard Schratt
Summary: This article investigates the plasticity mechanisms of neurons in the face of network activity disruptions. The study reveals that individual synapses are tagged for future strengthening during periods of chronic inactivity. These findings support the role of local mechanisms in homeostatic synaptic plasticity.
Article
Neurosciences
Anna Longatti, Luisa Ponzoni, Edoardo Moretto, Giorgia Giansante, Norma Lattuada, Maria Nicol Colombo, Maura Francolini, Mariaelvina Sala, Luca Murru, Maria Passafaro
Summary: Rho GTPases, specifically ARHGAP22, play a critical role in regulating actin dynamics and synaptic function in the CNS. Loss of ARHGAP22 leads to RAC1 hyperactivity and synaptic defects in dendritic spine density, molecular composition, and plasticity, resulting in cognitive impairment and reduced anxiety-like behavior in mice. Inhibiting RAC1 activity restores synaptic plasticity in ARHGAP22 KO mice, highlighting the importance of ARHGAP22 in hippocampal excitatory synapse formation and function, as well as in learning and memory behaviors.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jing Dong, Hui Fu, Yuanyuan Fu, Mingdan You, Xudong Li, Chaonan Wang, Kunkun Leng, Yuan Wang, Jie Chen
Summary: Exposure to DEHP during pregnancy can impair hippocampal synaptic plasticity in male offspring, affecting synaptic structure and dendritic spine development, possibly through the downregulation of the Rac1/PAK/LIMK1/cofilin signaling pathway. Female offspring did not show these alterations in hippocampal structure.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Cell Biology
Xianlin Zhu, Fan Zhang, Yufeng You, Hongbai Wang, Su Yuan, Banglin Wu, Rongyu Zhu, Dawei Liu, Fuxia Yan, Zaiping Wang
Summary: The study found that S-Ketamine can improve depression-like behavior in stressed rats by up-regulating the expression and activity of Rac1, increasing spine density and the expression of synaptic-related proteins, and reducing LTP impairments.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Mihika Bose, Mohammad Sarfaraz Nawaz, Rakhi Pal, Sumantra Chattarji
Summary: There is evidence for opposite effects of stress on synaptic plasticity in the hippocampus and amygdala, which is mediated by dysregulation of the Rac1-to-cofilin signaling pathway. Chronic stress leads to a loss of dendritic spines in the hippocampus, while promoting spinogenesis in the amygdala. These findings highlight the importance of brain-region specific differences in stress-induced plasticity for the development of stress-related psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biology
Christian Keine, Mohammed Al-Yaari, Tamara Radulovic, Connon Thomas, Paula Valino Ramos, Debbie Guerrero-Given, Mrinalini Ranjan, Holger Taschenberger, Naomi Kamasawa, Samuel M. Young
Summary: This study reveals the key regulatory role of Rac1 in synaptic transmission, mainly through modulating the dynamics of synaptic vesicle priming and potentially the release probability, affecting synaptic strength and short-term plasticity.
Article
Chemistry, Multidisciplinary
Guang-ying Li, Qiu-zi Wu, Tian-jia Song, Xue-chu Zhen, Xiang Yu
Summary: Normal brain function relies on the complex neural network, which is formed and maintained through synaptogenesis and synaptic plasticity. Deficiency in growth hormone can lead to brain development abnormalities and impair learning and memory, while growth hormone replacement therapy has been shown to ameliorate cognitive deficits. However, the underlying mechanism is still largely unknown.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Biochemistry & Molecular Biology
Balaganesh Kuruba, Nickolas Starks, Mary Rose Josten, Ori Naveh, Gary Wayman, Marina Mikhaylova, Alla S. Kostyukova
Summary: Dendritic spines, actin-rich protrusions that receive signals from axons at synapses, are affected by remodeling of cytoskeletal actin. Tropomodulin 2 (Tmod2), a brain-specific isoform, plays a role in regulating dendritic spine re-organization by binding to the pointed end of actin filaments through actin and tropomyosin binding sites. Overexpression of Tmod2 decreases spine number and increases spine length, and disrupting its binding abilities affects spine motility and stability.
Article
Multidisciplinary Sciences
Monika Jozsa, Tihol Ivanov Donchev, Rodolphe Sepulchre, Timothy O'Leary
Summary: Research has shown that a self-regulating signaling motif can generate reliable size-regulated switches by exploiting the breakdown of mass-action kinetics in chemical reaction systems. In synaptic and other small compartments, fluctuations are large due to low copy numbers of species, leading to a different behavior than typical mass-action kinetics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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.
Article
Neurosciences
Ali Ozgur Argunsah, Inbal Israely
Summary: Dendritic spines are highly dynamic structures that can undergo structural and functional fluctuations influenced by multiple factors. This study demonstrates that unstimulated neighboring spines can also experience structural modifications, which are dependent on the temporal pattern of plasticity-inducing stimulus. The findings suggest that activity patterns at single dendritic spines can shape plasticity at nearby synapse clusters, potentially priming local inputs for further modifications.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Shirin Hosseini, Marco van Ham, Christian Erck, Martin Korte, Kristin Michaelsen-Preusse
Summary: This study reveals the importance of alpha-tubulin tyrosination in controlling proper network formation and synaptic plasticity in the adult brain. The conditional deletion of TTL leads to incomplete development of the corpus callosum and anterior commissures, as well as deficits in spatial learning, impaired synaptic plasticity, and reduced spine number in hippocampal neurons.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
B. A. Kermath, A. M. Vanderplow, K. J. Bjornson, E. N. Seablom, A. M. Novak, C. R. Bernhardt, M. E. Cahill
Summary: The neural molecular and biochemical response to stress is a distinct physiological process, with the prefrontal cortex being particularly sensitive to stress. The Rap1 small GTPase pathway has emerged as a commonly disrupted intracellular target in neuropsychiatric conditions. Stress, through PFC dysfunction and Rap1 alterations, plays a critical role in cognitive impairment and synaptic phenotypes.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Sehyoun Yoon, Nicolas H. Piguel, Natalia Khalatyan, Leonardo E. Dionisio, Jeffrey N. Savas, Peter Penzes
Summary: Homer1, a synaptic scaffold protein, plays a role in regulating spine morphology and glutamatergic synapses. Lack of Homer1 leads to global reshaping of the synaptic proteome, characterized by upregulation of synaptic proteins. Interactions between Homer1 and proteins like ankyrin-G affect spine head size and stability.
MOLECULAR PSYCHIATRY
(2021)
Article
Neurosciences
Amanda M. Vanderplow, Andrew L. Eagle, Bailey A. Kermath, Kathryn J. Bjornson, Alfred J. Robison, Michael E. Cahill
Summary: The study found reduced Akt-mTOR PFC signaling in bipolar disorder subjects, which was associated with alterations in synaptic connectivity and function, leading to key cognitive phenotypes.
Article
Neurosciences
M. Dolores Martin-de-Saavedra, Marc Dos Santos, Lorenza Culotta, Olga Varea, Benjamin P. Spielman, Euan Parnell, Marc P. Forrest, Ruoqi Gao, Sehyoun Yoon, Emmarose McCoig, Hiba A. Jalloul, Kristoffer Myczek, Natalia Khalatyan, Elizabeth A. Hall, Liam S. Turk, Antonio Sanz-Clemente, Davide Comoletti, Stefan F. Lichtenthaler, Jeffrey S. Burgdorf, Maria V. Barbolina, Jeffrey N. Savas, Peter Penzes
Summary: The sheddome analysis in human cerebrospinal fluid (hCSF) identifies neuronal ectodomain shedding (ES) as an important mechanism in neurodevelopmental disorders. CNTNAP2-ecto, a prominent risk factor for neurodevelopmental disorders, undergoes activity-dependent shedding and its levels are reduced in individuals with autism spectrum disorder. The shed ectodomain of CNTNAP2 enhances the activity of PMCA2 and regulates neuronal network dynamics.
Article
Biochemistry & Molecular Biology
Amanda T. Vanderplow, Bailey N. Kermath, Cassandra B. Bernhardt, Kimberly C. Gums, Erin V. Seablom, Abigail L. Radcliff, Andrea J. Ewald, Mathew E. Jones, Tracy Baker, Jyoti Watters, Michael Cahill
Summary: Mounting evidence suggests that psychiatric disorders are influenced by genetics and early life experiences. Sleep apnea during pregnancy is increasingly common and can cause adverse outcomes. The long-term effects of maternal sleep apnea on offspring's brain-based behaviors and neuronal functioning are still unknown.
Review
Neurosciences
Lachlan A. Jolly, Raman Kumar, Peter Penzes, Michael Piper, Jozef Gecz
Summary: This review discusses the roles and importance of deubiquitinating enzymes (DUBs) in neurodevelopmental disorders (NDDs). Current genetic evidence and functional studies show that DUBs are associated with various NDDs and their study provides insights into protein degradation during brain development. The regulation of protein networks by DUBs and their connection to NDD genes offer opportunities for developing new therapeutic approaches.
BIOLOGICAL PSYCHIATRY
(2022)
Review
Neurosciences
Dolores Martin-de-Saavedra, Marc Dos Santos, Peter Penzes
Summary: This article provides an overview of the importance of ectodomain shedding in the nervous system, discussing the role of synaptic ectodomain shedding in autocrine and paracrine signaling. The article also highlights the use of cerebrospinal fluid analysis for identifying potential biomarkers for neuropsychiatric disorders.
TRENDS IN NEUROSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Brianna K. Unda, Leon Chalil, Sehyoun Yoon, Savannah Kilpatrick, Courtney Irwin, Sansi Xing, Nadeem Murtaza, Anran Cheng, Chad Brown, Alexandria Afonso, Elizabeth McCready, Gabriel M. Ronen, Jennifer Howe, Aurelie Caye-Eude, Alain Verloes, Brad W. Doble, Laurence Faivre, Antonio Vitobello, Stephen W. Scherer, Yu Lu, Peter Penzes, Karun K. Singh
Summary: Copy number variations (CNVs) are associated with psychiatric and neurodevelopmental disorders (NDDs), and the underlying disease mechanisms for most CNVs are unknown. In this study, a 15q13.3 microdeletion mouse model and patient iPSC-derived neurons were used to investigate the developmental defects caused by the CNV. By targeting the 15q13.3 CNV genetic driver OTUD7A, the study revealed a critical OTUD7A-Ankyrin pathway in neuronal development and dysfunction in the 15q13.3 microdeletion syndrome.
MOLECULAR PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Jeffrey S. Burgdorf, Sehyoun Yoon, Marc Dos Santos, Catherine R. Lammert, Joseph R. Moskal, Peter Penzes
Summary: We developed a peptide fragment JB2 that promotes synaptic plasticity and has therapeutic potential for Phelan-McDermid Syndrome and Autism Spectrum Disorder (ASD).
MOLECULAR PSYCHIATRY
(2023)
Review
Neurosciences
Colleen R. Zaccard, Isabel Gippo, Amy Song, Changiz Geula, Peter Penzes
Summary: Dendritic spines, including dendritic spinules, play a crucial role in structural synaptic plasticity related to cognition and memory. Spinules are fine membranous protrusions that can contact neighboring cells and are regulated by neuronal activity. Recent studies have shown that spinules are smaller, short-lived, and dynamic, with potential roles in exploring the environment and mediating signaling and membrane remodeling.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Euan Parnell, Roos A. A. Voorn, M. Dolores Martin-de-Saavedra, Daniel D. D. Loizzo, Marc Dos Santos, Peter Penzes
Summary: In this study, a Kalirin-7 missense mutation associated with severe developmental delay was identified. The mutation resulted in reduced Kalirin-7 function, leading to impaired neuroarchitecture and connectivity, which may contribute to developmental delay in the patient.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Marc P. Forrest, Marc Dos Santos, Nicolas H. Piguel, Yi-Zhi Wang, Nicole A. Hawkins, Vikram A. Bagchi, Leonardo E. Dionisio, Sehyoun Yoon, Dina Simkin, Maria Dolores Martin-de-Saavedra, Ruoqi Gao, Katherine E. Horan, Alfred L. George Jr, Mark S. LeDoux, Jennifer A. Kearney, Jeffrey N. Savas, Peter Penzes
Summary: This study reveals that the 16p11.2 duplication increases the risk of autism and schizophrenia, and proteomics analysis shows that it causes dysregulation of synaptic and epilepsy-associated protein networks. The authors also demonstrate that correcting Prrt2 gene dosage can rescue circuit hypersynchrony and behavioral phenotypes. These findings contribute to our understanding of the biological basis of neuropsychiatric disorders and epilepsy.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Nicolas H. Piguel, Shaun S. Sanders, Francesca I. De Simone, Maria D. Martin-de-Saavedra, Emmarose McCoig, Leonardo E. Dionisio, Katharine R. Smith, Gareth M. Thomas, Peter Penzes
Summary: This study found that palmitoylation of AnkG-190 at Cys70 stabilizes its localization in spine heads and dendritic plasma membrane nanodomains. Mutation of Cys70 impairs the function of AnkG-190 in dendritic spines and alters PSD-95 scaffolding. Furthermore, lithium reduces the palmitoylation of AnkG-190, resulting in increased mobility in dendritic spines. The findings highlight the critical role of palmitoylation in AnkG-190 and provide insights into the ZDHHC8/AnkG-190 mechanism linking lithium effects in neurons.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Kathryn J. Bjornson, Amanda M. Vanderplow, Yezi Yang, Danielle R. Anderson, Bailey A. Kermath, Michael E. Cahill
Summary: This study found that repeated stress leads to increased levels of synaptic Rapt protein in the hippocampal region, resulting in changes in dendritic spines and cognitive phenotypes. By using super resolution imaging, the study revealed how the Rapt protein affects the stability of specific dendritic spines. These findings highlight the involvement of aberrant Rapt regulation in the hippocampus in contributing to the psychobiological effects of stress.
Review
Biochemistry & Molecular Biology
Sehyoun Yoon, Nicolas H. Piguel, Peter Penzes
Summary: Ankyrin-G protein plays an essential role in regulating cellular functions and its mutations are associated with various neuropsychiatric disorders. Understanding the expression patterns, posttranslational modifications, and interactions of ankyrin-G with other brain proteins can reveal potential mechanisms underlying these diseases.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
