Article
Multidisciplinary Sciences
Maria Casas, Karl D. Murray, Keiko Hino, Nicholas C. Vierra, Sergi Simo, James S. Trimmer, Rose E. Dixon, Eamonn J. Dickson
Summary: The loss of NPC1 function alters the nanoscale distribution and function of ion channels, leading to abnormal calcium entry, mitochondrial dysfunction, and neurotoxicity. These findings provide insights into the molecular mechanisms connecting NPC1 loss to NPC-associated neuropathology.
NATURE COMMUNICATIONS
(2023)
Article
Agronomy
Claudia Bonomelli, Sergio Tonetto de Freitas, Camila Aguilera, Carola Palma, Rebeca Garay, Maximiliano Dides, Natalia Brossard, Jose Antonio O'Brien
Summary: Proper nitrogen and calcium fertilization management is vital for crop growth, as an imbalance between these elements can lead to physiological and yield issues. Tomato plants are particularly susceptible to nutritional imbalances, emphasizing the importance of maintaining a balance between nitrogen and calcium. Monitoring the Ca/N ratio can serve as a key indicator for appropriate nutrient levels and overall plant health in tomato production.
Article
Neurosciences
Robin N. Stringer, Leos Cmarko, Gerald W. Zamponi, Michel De Waard, Norbert Weiss
Summary: T-type calcium channelopathies are a group of human disorders caused or exacerbated by mutations in genes encoding T-type calcium channels. A new mutation in the CACNA1H gene encoding the Ca(v)3.2 T-type calcium channel was found in a patient with epilepsy and hearing loss, the first CACNA1H mutation associated with a sensorineural hearing condition. This mutation results in minor gating alterations and enhanced sensitivity to external pH change in the channel.
Article
Cardiac & Cardiovascular Systems
Brian D. Tow, Arpita Deb, Shraddha Neupane, Shuchi M. Patel, Meagan Reed, Anna-Beth Loper, Roman A. Eliseev, Bjorn C. Knollmann, Sandor Gyorke, Bin Liu
Summary: In this study, the interaction between sarcoplasmic reticulum (SR) and mitochondria was found to play a crucial role in shaping divergent cardiac pathologies. Mitochondria in the CPVT2 model buffered SR-derived diastolic Ca release to mitigate pathological remodeling, while utilizing mPTP-mediated Ca efflux to avoid excess mitochondrial Ca overload, in contrast to the FFD model which was more susceptible to mtROS-dependent RyR2 leak. Pharmacological and genetic manipulation of mitochondrial Ca handling pathways revealed differential effects on disease phenotypes, highlighting the importance of SR-mitochondria interplay in regulating intracellular Ca signaling and cardiac pathologies.
CARDIOVASCULAR RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Kaihui Lu
Summary: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by metabolic disorders in the liver. It is characterized by hyperammonemia, EEG abnormalities, and disturbances in sensory, motor, and cognitive functions. The main mechanisms of HE include ammonia poisoning, oxidative/nitrosative stress, manganese toxicity, autophagy inhibition, mitochondrial damage, inflammation, and senescence.
Review
Oncology
Shane O'Grady, Maria P. Morgan
Summary: The Ca2+ signalling network is crucial for normal cellular activities and is frequently altered in breast cancer, driving tumorigenesis. Understanding these pathways may offer clinical benefit in terms of prognosis and treatment, providing potential therapeutic targets.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Physiology
Elizabeth J. Akin, Joydeep Aoun, Connor Jimenez, Katie Mayne, Julius Baeck, Michael D. Young, Brennan Sullivan, Kenton M. Sanders, Sean M. Ward, Simon Bulley, Jonathan H. Jaggar, Scott Earley, Iain A. Greenwood, Normand Leblanc
Summary: In pulmonary arterial smooth muscle cells, ANO1, Ca(V)1.2, and IP3R play a role in generating vascular tone by regulating Ca2+ release and oscillations. These channels are involved in the stable contraction and intracellular Ca2+ signaling in response to agonists.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Neurosciences
Zhendong Feng, Oleg O. Glebov
Summary: This study reveals how neuronal activity rapidly regulates the recruitment of R-type VGCCs in hippocampal neurons through synaptic NMDAR signaling, suggesting a feedback mechanism for regulating synaptic Ca2+ signaling.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Chien-Wen S. Kuo, Sara Dobi, Caglar Goek, Ana Da Silva Costa, Alice Main, Olivia Robertson-Gray, Daniel Baptista-Hon, Krzysztof J. Wypijewski, Hannah Costello, Tim G. Hales, Niall MacQuaide, Godfrey L. Smith, William Fuller
Summary: The α1C subunit of L-type Ca2+ channels, responsible for transmembrane Ca2+ fluxes, undergoes reversible palmitoylation in rat, rabbit, and human ventricular myocytes. The sites of palmitoylation are found in the N terminus and the linker between domains I and II of the channel. Unpalmitoylated α1C subunit leads to reduced voltage sensitivity of Ca2+ channels.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Blanca Calle-Ciborro, Teresa Espin-Jaime, Francisco J. Santos, Ana Gomez-Martin, Isaac Jardin, Maria J. Pozo, Juan A. Rosado, Pedro J. Camello, Cristina Camello-Almaraz
Summary: Skeletal muscle releases hormones called myokines, which interact with other organs and mediate the effects of physical activity. The release of interleukin 6 (IL-6), a myokine involved in inflammation, immunity, and metabolism, from muscle cells is not well understood. This study investigated the role of calcium ions in the release of IL-6 from human muscle cells and found that proteins responsible for calcium increase during stimulation induce IL-6 release. These findings could provide insights into the release of IL-6 and other myokines in pathological conditions.
Article
Biochemistry & Molecular Biology
Marena Montera, Aleyah Goins, Leos Cmarko, Norbert Weiss, Karin N. Westlund, Sascha R. A. Alles
Summary: The study demonstrates the involvement of the Ca(v)3.3 T-type voltage-gated calcium channel subtype in chronic trigeminal neuropathic pain and suggests that blocking or attenuating its function may be an effective strategy for treatment. Furthermore, the results indicate that targeting Ca(v)3.3 could be more effective in female mice with trigeminal neuropathic pain in the FRICT-ION model.
Article
Biochemistry & Molecular Biology
Suk-Young Song, Soonil Pyo, Sungchul Choi, Hee Sang Oh, Jung Hwa Seo, Ji Hea Yu, Ahreum Baek, Yoon-Kyum Shin, Hoo Young Lee, Ja Young Choi, Sung-Rae Cho
Summary: Environmental enrichment (EE) has a significant therapeutic effect on HIE, upregulating the expression of the Ca-v 2.1 channel and presynaptic proteins, leading to improvements in motor and cognitive performance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Oezguer Celik, Fatih Yergoez, Christof Schuette, Christoph Stein, Marcus Weber, Stefanie Winkelmann
Summary: We have successfully designed, synthesized, and tested the prototype opioid painkiller NFEPP, which does not have adverse side effects. The design process was based on mathematical modeling of interactions between G-protein coupled receptors (GPCRs) and ligands, considering the different functions of GPCRs under pathological and healthy conditions. Additionally, we have proposed a novel stochastic model of GPCR function that takes into account intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels, which depend on the parameters of inflamed and healthy tissue (pH, radicals). The model has been validated using in vitro experimental data for NFEPP and fentanyl at different pH values and radical concentrations.
SCIENTIFIC REPORTS
(2023)
Article
Pharmacology & Pharmacy
Patrick Despang, Sarah Salamon, Alexandra Breitenkamp, Elza Kuzmenkina, Jan Matthes
Summary: In this study, we characterized a novel variant of Ca-V beta(1b) identified in an ASD patient. Our results showed that this variant inhibits the function of L- and N-type VGCCs, but maintains its interaction with and modulation by the RGK-protein Gem. Our findings suggest functional effects of this Ca-V beta(1b_R296C) variant different from the Ca-V beta(2) variants found in ASD patients.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Volker Herzig, Yong-Cyuan Chen, Yanni K-Y Chin, Zoltan Dekan, Yu-Wang Chang, Hui-Ming Yu, Paul F. Alewood, Chien-Chang Chen, Glenn F. King
Summary: This study identified a tarantula venom from Avicularia spec. that can inhibit specific subtypes of T-type calcium channels, with the active toxin being omega-Avsp1a. The research suggests that omega-Avsp1a can inhibit specific subtypes of T-type calcium channels, and the domain-1 of Ca(V)3.3 is crucial for this inhibitory effect.
Article
Biology
Marcus Augusto-Oliveira, Gabriela P. Arrifano, Charlotte Isabelle Delage, Marie-Eve Tremblay, Maria Elena Crespo-Lopez, Alexei Verkhratsky
Summary: Microglial cells, originating from foetal macrophages, undergo phenotypic metamorphosis in response to the nervous tissue environment, displaying high plasticity and heterogeneity in gene and protein expression; their surveilling functions are crucial for maintaining homeostasis and contributing to the adaptive capacity of the central nervous system.
BIOLOGICAL REVIEWS
(2022)
Article
Clinical Neurology
Ting Du, Humberto Mestre, Benjamin T. Kress, Guojun Liu, Amanda M. Sweeney, Andrew J. Samson, Martin Kaag Rasmussen, Kristian Nygaard Mortensen, Peter A. R. Bork, Weiguo Peng, Genaro E. Olveda, Logan Bashford, Edna R. Toro, Jeffrey Tithof, Douglas H. Kelley, John H. Thomas, Poul G. Hjorth, Erik A. Martens, Rupal Mehta, Hajime Hirase, Yuki Mori, Maiken Nedergaard
Summary: Cerebral edema develops after anoxic brain injury and is associated with the availability of cerebrospinal fluid (CSF). An increase in CSF volume worsens the severity of edema. Edema primarily occurs in brain regions bordering CSF compartments. Anoxic brain tissue possesses a high intrinsic osmotic potential, which may contribute to the beneficial effect of therapeutic hypothermia.
Editorial Material
Cell Biology
Alexei Verkhratsky, Alexey Semyanov
Article
Biochemistry & Molecular Biology
Ya-Fei Zhao, Wen-Jing Ren, Ying Zhang, Jin-Rong He, Hai-Yan Yin, Yang Liao, Patrizia Rubini, Jan M. Deussing, Alexei Verkhratsky, Zeng-Qiang Yuan, Peter Illes, Yong Tang
Summary: This study suggests that P2X7 receptors in hippocampal astrocytes are involved in the development of depressive disorder, and microglia and astrocytes respond differently to stress stimuli.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Multidisciplinary Sciences
Alexei Verkhratsky, Margaret S. Ho, Vladimir Parpura, Aleksandra Pekowska
Summary: The evolution of the nervous system involved cellular diversification and specialization of functions, with the emergence of the centralized nervous system leading to an increase in the complexity of neuroglia. In the primate brain, especially in humans, the astrocyte lineage is exceedingly complex, possibly facilitating interlayer communication and integration.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Robert Zorec, Alexei Verkhratsky
Summary: Astrocytes are key homeostasis providing cells in the central nervous system, and their alterations are associated with diseases caused by infectious insults. Neurotropic infections, including COVID-19 and other viruses, activate astrocytes and utilize their metabolic characteristics for viral multiplication. However, the failure of astrocyte protection in certain circumstances remains a topic for future study.
ESSAYS IN BIOCHEMISTRY
(2023)
Review
Neurosciences
Guojun Liu, Antonio Ladron-de-Guevara, Yara Izhiman, Maiken Nedergaard, Ting Du
Summary: Cerebrospinal fluid (CSF) is a critical component of the central nervous system, providing protection and transport functions. However, there is limited knowledge about its production rate and the impact of diseases on CSF dynamics. This review aims to highlight the importance of quantifying CSF production and inspire the development of more accurate and less invasive measurement techniques.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Review
Physiology
Chia-Yu Yeh, Kuan-Yu Wu, Guo-Jen Huang, Alexei Verkhratsky
Summary: Adult neurogenesis is an important process that contributes to adaptive network remodelling in the brain. This review focuses on the cellular characteristics and roles of radial astrocytes (RSA) and parenchymal astrocytes in adult neurogenesis in different brain regions. The potential therapeutic applications of RSA and astrocytes in cell replacement and regeneration strategies are also discussed.
Editorial Material
Physiology
Alan Alpar, Alexei Verkhratsky
Article
Biochemistry & Molecular Biology
Xinyu Li, Binjie Chen, Dianjun Zhang, Siman Wang, Yuliang Feng, Xiafang Wu, Lulu Cui, Ming Ji, Wenliang Gong, Alexei Verkhratsky, Maosheng Xia, Baoman Li
Summary: A novel mouse model of mania was developed by exposing mice to chronic unpredictable rhythm disturbances (CURD), including disruption of circadian rhythm, sleep deprivation, exposure to bright light, and other stressors. The CURD mice exhibited manic behaviors similar to those observed in patients with manic syndrome. Treatment with LiCl and valproic acid improved behaviors and molecular indicators in the manic mice. This environment-based model provides a valuable tool for studying the neuropathological mechanisms of mania.
MOLECULAR PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Kimberly A. S. Boster, Shengze Cai, Antonio Ladron-de-Guevara, Jiatong Sun, Xiaoning Zheng, Ting Du, John H. Thomas, Maiken Nedergaard, George Em Karniadakis, Douglas H. Kelley
Summary: This study demonstrates the use of artificial intelligence velocimetry (AIV) to quantify the flow of cerebrospinal fluid (CSF) in pial perivascular spaces (PVSs) by integrating sparse velocity measurements with physics-informed neural networks. AIV infers three-dimensional high-resolution velocity, pressure, and shear stress, and the results are validated and analyzed for sensitivity. The findings contribute to improving fluid dynamic models and potentially providing insights into how CSF flow changes in aging, Alzheimer's disease, and small vessel disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Si-Si Lin, Bin Zhou, Bin-Jie Chen, Ruo-Tian Jiang, Baoman Li, Peter Illes, Alexey Semyanov, Yong Tang, Alexei Verkhratsky
Summary: This study found that electroacupuncture can prevent atrophy of astrocytes in the prefrontal cortex, and alleviate depressive-like behavior induced by chronic unpredictable mild stress. These behavioral changes are associated with morphological atrophy of astrocytes and down-regulation of the protein Ezrin.
CELL DEATH & DISEASE
(2023)
Editorial Material
Cell Biology
Alexei Verkhratsky, Alexey Semyanov
Summary: Lia et al. discovered the critical role of the STIM1 ER Ca2+ sensor in the functional decline of astrocytes in AD-like pathology in PS2APP mice. The downregulation of STIM1 expression in astrocytes resulted in decreased ER Ca2+ content and impaired astrocytic Ca2+ signaling, leading to synaptic and memory deficits. Overexpression of STIM1 in astrocytes restored Ca2+ excitability and improved synaptic and memory function.
Review
Neurosciences
Chenju Yi, Alexei Verkhratsky, Jianqin Niu
Summary: Adult oligodendrocyte precursor cells (aOPCs), derived from fetal OPCs, are unique neuroglia cells in the central nervous system (CNS) and have diverse roles in neurological diseases. This review presents the physiology of aOPCs and summarizes the beneficial and detrimental effects of aOPCs in different CNS diseases. The paper discusses aOPC death, reactivity, changes during senescence, interactions with other glial cells, and pathological remodeling during disease, and outlines future perspectives for studying aOPCs in brain pathologies for potential therapeutic strategies.
TRENDS IN NEUROSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alexei Verkhratsky, Arthur Butt, Baoman Li, Peter Illes, Robert Zorec, Alexey Semyanov, Yong Tang, Michael V. Sofroniew
Summary: This article introduces the pathophysiology of astroglial cells in neurological diseases and disorders, discussing their changes and functions in different pathological states, and proposes the identification of cellular and molecular mechanisms of astroglial pathophysiology as a new frontier for finding novel therapeutic strategies.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Physiology
Minyu Zhang, Biyang Xiao, Xiaoqi Chen, Bingming Ou, Songtao Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) is closely related to bile acid and gut microbiota disorders. Exercise plays an important role in maintaining the homeostasis of the enterohepatic circulation and the health of the host gut microbiota by regulating the composition and function of the bile acid pool in the enterohepatic axis. Exercise has been recommended as a first-line intervention for NAFLD, and regulating bile acids through exercise may be a promising treatment strategy.