Review
Neurosciences
Octavio Garcia, Lisi Flores-Aguilar
Summary: Down syndrome is caused by the triplication of human chromosome 21, leading to intellectual disability. Individuals with DS may develop clinical symptoms associated with Alzheimer's disease in middle adulthood.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ian D. Blum, Mehmet F. Keles, El-Sayed Baz, Emily Han, Kristen Park, Skylar Luu, Habon Issa, Matt Brown, Margaret C. W. Ho, Masashi Tabuchi, Sha Liu, Mark N. Wu
Summary: Sleep is regulated by astroglial Ca2+ signaling that increases with sleep need in Drosophila. A genetic screen identified TyrRII receptor as crucial for sleep homeostasis. These findings reveal important mechanisms involved in encoding and regulating sleep need.
Article
Biology
Knut Sindre abjorsbraten, Gry H. E. Syverstad Skaaraas, Celine Cunen, Daniel M. Bjornstad, Kristin M. Gullestad Binder, Laura Bojarskaite, Vidar Jensen, Lars N. G. Nilsson, Shreyas B. Rao, Wannan Tang, Gudmund Horn Hermansen, Erlend A. Nagelhus, Ole Petter Ottersen, Reidun Torp, Rune Enger
Summary: Increased astrocytic Ca2+ signaling has been observed in Alzheimer's disease mouse models. In this study, we investigated behaviorally induced astrocytic Ca2+ signaling in plaque-bearing mice and found an attenuated response to locomotion and a decoupling of pupil responses and astrocytic Ca2+ signaling. We also observed reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic explanation for the reduced astrocytic Ca2+ responses. Our findings suggest a dysfunction in the norepinephrine-astrocyte Ca2+ activity axis, which may contribute to cognitive deficits in Alzheimer's disease.
Review
Neurosciences
Xiaomin Huang, Yixun Su, Nan Wang, Hui Li, Zhigang Li, Guowei Yin, Hui Chen, Jianqin Niu, Chenju Yi
Summary: Astrocytes play a crucial role in maintaining the normal functions of the Central Nervous System (CNS). During neurodegenerative diseases, alterations in astrocytic connexin expression and function can affect disease progression by impacting neuronal function and survival. Targeting connexins may be a plausible therapeutic strategy for managing these neurodegenerative diseases.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Geriatrics & Gerontology
Dibyadeep Datta
Summary: Aging rhesus macaques serve as an invaluable model for studying the etiological mechanisms of sporadic Alzheimer's disease (AD) and exploring novel therapeutic strategies. These macaques naturally exhibit amyloid and tau pathology, synaptic dysfunction, and cognitive impairments similar to human AD. Unique molecular mechanisms in the newly evolved primate dorsolateral prefrontal cortex, involving feedforward cyclic adenosine monophosphate (cAMP)-Protein kinase A (PKA)-calcium signaling, play a critical role in higher-order cognition. However, genetic predispositions and age-related insults can exacerbate these signaling pathways and lead to downstream effects, increasing susceptibility to atrophy.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Melania Gonzalez-Rodriguez, Veronica Astillero-Lopez, Patricia Villanueva-Anguita, M. Eugenia Paya-Rodriguez, Alicia Flores-Cuadrado, Sandra Villar-Conde, Isabel Ubeda-Banon, Alino Martinez-Marcos, Daniel Saiz-Sanchez
Summary: Alzheimer's disease is the most prevalent neurodegenerative disease in the elderly, characterized by the accumulation of A beta and tau proteins. The expression of somatostatin may play a role in the pathogenesis of Alzheimer's disease, particularly with a significant reduction in the human hippocampus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Victor Tapias, Paula Gonzalez-Andres, Laura F. Pena, Asuncion Barbero, Lucia Nunez, Carlos Villalobos
Summary: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases in the elderly, characterized by abnormal protein aggregates and loss of neurons in specific brain regions. The exact mechanisms of these diseases are unknown, but oxidative stress, mitochondrial dysfunction, and disrupted Ca2+ homeostasis play a crucial role. With an increase in life expectancy, there is a need for preventive strategies and disease-modifying therapies for AD/PD. Modulating Ca2+ homeostasis and signaling, as well as controlling mitochondrial function with heterocyclic compounds, may provide potential neuroprotective treatments for these diseases.
Review
Cell Biology
Dong-Xu Huang, Xin Yu, Wen-Jun Yu, Xin-Min Zhang, Chang Liu, Hong-Ping Liu, Yue Sun, Zi-Ping Jiang
Summary: The precise regulation of calcium ion by neurons is essential for cellular signaling and survival, with calcium homeostasis maintained by both endoplasmic reticulum and mitochondria. Dysregulation of calcium signaling is associated with Alzheimer's disease, highlighting the importance of understanding the cellular and molecular mechanisms underlying calcium regulation in neurodegenerative diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Neurosciences
Pooja Jadiya, Joanne F. Garbincius, John W. Elrod
Summary: The cellular and molecular mechanisms underlying neurodegeneration are still poorly understood, but recent studies have shown that mitochondrial and calcium dysregulation occur early in many NDDs, providing new insights into the pathogenesis. Defective mitochondrial metabolism may play a crucial role in the diverse etiologies of neuropathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Clinical Neurology
Steve Reiken, Leah Sittenfeld, Haikel Dridi, Yang Liu, Xiaoping Liu, Andrew R. Marks
Summary: This study provided evidence linking SARS-CoV-2 infection to TGF-beta signaling activation and oxidative overload in COVID-19 patients, as well as the activation of neuropathological pathways associated with AD. The leaky phenotype of RyR2 in COVID-19 brains may contribute to cognitive and behavioral defects. Targeting leaky RyR2 channels could potentially be a therapeutic strategy for alleviating cognitive impairments associated with SARS-CoV-2 infection and long COVID.
ALZHEIMERS & DEMENTIA
(2022)
Review
Biochemistry & Molecular Biology
Tadahiro Numakawa, Haruki Odaka
Summary: Neurotrophins play crucial roles in supporting neuronal survival, synaptic plasticity, and neurogenesis in the nervous system. The decline of cognitive function with aging and/or pathological conditions is associated with alterations in BDNF/TrkB signaling. Upregulation of the endogenous BDNF/TrkB system may be a potential therapeutic approach for cognitive decline.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Nikita Arnst, Nelly Redolfi, Annamaria Lia, Martina Bedetta, Elisa Greotti, Paola Pizzo
Summary: Alzheimer's disease is a neurodegenerative illness characterized by the loss of neurons in specific brain areas. The calcium hypothesis is at the forefront of current research as a potential key pathway in Alzheimer's disease.
Article
Immunology
T. L. Stephen, B. Breningstall, S. Suresh, C. J. McGill, C. J. Pike
Summary: The APOE genotype and biological sex have effects on AD pathogenesis, particularly in the interactions between astrocytes and amyloid plaques.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Beatriz Pacheco-Sanchez, Ruben Tovar, Meriem Ben Rabaa, Lourdes Sanchez-Salido, Antonio Vargas, Juan Suarez, Fernando Rodriguez de Fonseca, Patricia Rivera
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease in which astrocytes and the endocannabinoid system (ECS) play important roles. The study focuses on the cannabinoid signaling machinery in hippocampal astrocytes from 3xTg-AD mice to determine their involvement in the disease. The findings show low inflammatory activity, Ca2+ flow, and cannabinoid signaling in 3xTg-AD hippocampal astrocytes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Christiaan F. M. Huffels, Roland E. van Dijk, Henk Karst, Frank J. Meye, Elly M. Hol, Jinte Middeldorp
Summary: The study demonstrates that blood-borne factors are sufficient to drive neurophysiological impairments in the hippocampal CA1, leading to impaired levels of long-term potentiation (LTP). These impairments are similar to those found in mouse models for AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Editorial Material
Cell Biology
Alexei Verkhratsky, Govindan Dayanithi
Summary: The day/night cycle affects neurogenesis, with melatonin released in darkness decreasing neural stem cell proliferation by stimulating intracellular Ca2+ dynamics. During the day, neural stem cell division is stimulated and the generation of newborn neurons is increased as intracellular Ca2+ activity subsides.
Review
Neurosciences
Carole Escartin, Elena Galea, Andras Lakatos, James P. O'Callaghan, Gabor C. Petzold, Alberto Serrano-Pozo, Christian Steinhauser, Andrea Volterra, Giorgio Carmignoto, Amit Agarwal, Nicola J. Allen, Alfonso Araque, Luis Barbeito, Ari Barzilai, Dwight E. Bergles, Gilles Bonvento, Arthur M. Butt, Wei-Ting Chen, Martine Cohen-Salmon, Colm Cunningham, Benjamin Deneen, Bart De Strooper, Blanca Diaz-Castro, Cinthia Farina, Marc Freeman, Vittorio Gallo, James E. Goldman, Steven A. Goldman, Magdalena Gotz, Antonia Gutierrez, Philip G. Haydon, Dieter H. Heiland, Elly M. Hol, Matthew G. Holt, Masamitsu Iino, Ksenia V. Kastanenka, Helmut Kettenmann, Baljit S. Khakh, Schuichi Koizumi, C. Justin Lee, Shane A. Liddelow, Brian A. MacVicar, Pierre Magistretti, Albee Messing, Anusha Mishra, Anna V. Molofsky, Keith K. Murai, Christopher M. Norris, Seiji Okada, Stephane H. R. Oliet, Joao F. Oliveira, Aude Panatier, Vladimir Parpura, Marcela Pekna, Milos Pekny, Luc Pellerin, Gertrudis Perea, Beatriz G. Perez-Nievas, Frank W. Pfrieger, Kira E. Poskanzer, Francisco J. Quintana, Richard M. Ransohoff, Miriam Riquelme-Perez, Stefanie Robel, Christine R. Rose, Jeffrey D. Rothstein, Nathalie Rouach, David H. Rowitch, Alexey Semyanov, Swetlana Sirko, Harald Sontheimer, Raymond A. Swanson, Javier Vitorica, Ina-Beate Wanner, Levi B. Wood, Jiaqian Wu, Binhai Zheng, Eduardo R. Zimmer, Robert Zorec, Michael V. Sofroniew, Alexei Verkhratsky
Summary: The article highlights the challenges and uncertainties surrounding reactive astrocytes, advocating for comprehensive research that includes assessment of multiple molecular and functional parameters, preferably in vivo, along with multivariate statistics and determination of impact on pathological hallmarks in relevant models.
NATURE NEUROSCIENCE
(2021)
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)
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
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
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)
Meeting Abstract
Endocrinology & Metabolism
Cihan Civan Civas, Sevgi Suna Karatay, Cihan Suleyman Erdogan, Alexei Verkhratsky, Bayram Yilmaz
NEUROENDOCRINOLOGY
(2021)