Article
Biochemistry & Molecular Biology
Mariko Kato Hayashi, Kaoru Sato, Yuko Sekino
Summary: Neurons induce astrocyte branches and make them avoid each other, potentially contributing to the tiling of astrocytes' territories.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Andres M. Baraibar, Lindsey Belisle, Giovanni Marsicano, Carlos Matute, Susana Mato, Alfonso Araque, Paulo Kofuji
Summary: Microcircuits in the neocortex are functionally organized along layers and columns, and astrocytes play a role in the functional organization and bidirectional interaction between neurons. Activation of astrocytes by endocannabinoids leads to an increase in Ca2+ levels, ATP/adenosine release, and temporary synaptic depression between layer 5 pyramidal neurons at relatively distant synapses. This form of heteroneuronal synaptic depression is specific to cortical columns and layers, depending on layer-specific neuron-to-astrocyte signaling.
Article
Neurosciences
Jun An, Yan He, Jun-Jun Yin, Zhi-Bin Ding, Qing-Xian Han, Yang-Yang Chen, Qing Wang, Zhi Chai, Jie-Zhong Yu, Li-Juan Song, Bao-Guo Xiao, Cun-Gen Ma
Summary: In the CPZ-induced mouse model, significant reduction of axons and neurons occurs 4-6 weeks after feeding, leading to neuronal death and loss of glutamate neurons. Astrocyte-mediated glutamate reuptake plays a protective role against excitotoxicity in the CNS.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marta Sidoryk-Wegrzynowicz, Beata Dabrowska-Bouta, Grzegorz Sulkowski, Lidia Struzynska
Summary: Tau-dependent neurodegeneration in a transgenic mouse model is accompanied by astrocytosis, indicating the critical role of astrocytes in the disease development. Alterations in glutamine transport and recycling affect the neuronal-astrocytic integrity, suggesting potential mechanisms operating in Tau pathology.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Review
Neurosciences
Xing Liu, Jun Ying, Xifeng Wang, Qingcui Zheng, Tiancheng Zhao, Sungtae Yoon, Wen Yu, Danying Yang, Yang Fang, Fuzhou Hua
Summary: Astrocytes are major glial cells in the brain, playing a supporting role in the energy and nutritional supply of neurons. They actively regulate synaptic transmission, formation, and plasticity, and any negative changes in their structure or function can impact neuronal activity, leading to neurodevelopmental disorders. Understanding the roles of astrocytes in regulating synaptic development and neural circuit plasticity could lead to new treatments for various neurological and psychiatric disorders.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Alexey Berezhnov, Evgeniya Fedotova, Alexander Sergeev, Ilya Y. Teplov, Andrey Y. Abramov
Summary: Dopamine plays a crucial role in neuronal modulation and signaling by inducing calcium signals in astrocytes to suppress spontaneous calcium oscillations in neurons. The effects of dopamine on neurons are dependent on astrocytic calcium signaling, GABA, and alpha-adrenoreceptors. This suggests that dopamine-induced calcium signals may stimulate release of neuromodulators like GABA and adrenaline to suppress neuronal oscillations.
Article
Developmental Biology
Osamu Nozawa, Muneaki Miyata, Hajime Shiotani, Takeshi Kameyama, Ryouhei Komaki, Tatsuhiro Shimizu, Toshihiko Kuriu, Yutaro Kashiwagi, Yuka Sato, Michinori Koebisu, Atsu Aiba, Shigeo Okabe, Kiyohito Mizutani, Yoshimi Takai
Summary: We demonstrated that co-cultured neurons induced astrocyte ramifications and formation of tripartite synapses in an in vitro system. The induction of astrocyte ramifications was dependent on neuronal activity and likely involved synaptically-released glutamate and activation of astrocytic mGluR5. Moreover, the Necl2/3 trans-interaction recruited glutamate transporters and K+ channels to the perisynaptic astrocyte processes, enhancing synapse formation and astrocyte functional polarization.
Article
Neurosciences
Duo Li, Sihui Li, Min Pan, Qiang Li, Jiangling Song, Rui Zhang
Summary: This study proposed a novel neuron-astrocyte computational model to investigate the impact of extracellular glutamate homeostasis dysregulation on neuronal epileptic discharges. The results demonstrated that downregulation of EAAT2 expression, aberrant activation of mGluRs, and elevated glutamate levels can aggravate neuronal epileptic discharges and transition between different discharge states. These factors can also alter the bifurcation threshold for the generation and transition of epileptic discharges.
COGNITIVE NEURODYNAMICS
(2023)
Review
Neurosciences
Ana Covelo, Abel Eraso-Pichot, Ignacio Fernandez-Moncada, Roman Serrat, Giovanni Marsicano
Summary: The endocannabinoid system plays a crucial role in various brain functions by activating CB1R, impacting synaptic activity and behavior. In recent years, astrocytes have been recognized as significant players in brain physiology due to their involvement in the tripartite synapse and metabolic interactions with neurons. Evidence suggests that astrocytes may serve as important sources of endocannabinoid synthesis and release, adding complexity to the understanding of ECS in brain functions.
Review
Biochemistry & Molecular Biology
Hagar Bauminger, Inna Gaisler-Salomon
Summary: This study discusses the role of glutamate homeostasis in schizophrenia-related cognitive dysfunction. They focus on cognitive domains that can be measured in humans and rodents, and discuss the relevance of glutamate alterations in these domains. They find that the interaction between astrocytes and neurons is crucial for cognition, and that presynaptic and postsynaptic components play a critical role in maintaining glutamate homeostasis and cognitive well-being.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Tianyou Wang, Yingqi Sun, Ulf Dettmer
Summary: Parkinson's disease is characterized by the loss of dopaminergic neurons. This review highlights the roles of astrocytes in PD and how their properties can be utilized to increase neuron survivability. Astrocytes normally have protective functions but can become dysfunctional and contribute to neurotoxicity in PD. Restoring healthy astrocyte function and maximizing their beneficial effects represent promising therapeutic approaches.
Article
Neurosciences
Elnaz Khezerlou, Neela Prajapati, Mark A. DeCoster
Summary: Glial cells play a crucial role in maintaining neuronal homeostasis and influencing excitability in epileptogenesis through negative feedback mechanisms. By imaging intracellular calcium concentration in different cell cultures, the study demonstrates the role of glial cells in providing negative feedback. The research also highlights the importance of the order of stimuli in predicting cellular responses, especially in networks with low negative feedback.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Ke-Xin Li, Meng Lu, Meng-Xu Cui, Xiao-Ming Wang, Yang Zheng
Summary: The study aimed to investigate the regulatory mechanisms of the Notch pathway in mediating glutamate transport and synaptic plasticity. The findings showed that in the early stage of hypoxic ischemic injury, glutamate transporter expression was downregulated and synaptic vesicle number decreased. However, activation of the Notch pathway after 12-24 hours led to an increase in glutamate transporter expression and synaptic vesicle number. Inhibition of the Notch pathway resulted in decreased expression of glutamate transporter and synaptophysin. These results suggest that glutamate transport in astrocytes-neurons after hypoxic ischemic injury is regulated by the Notch pathway and affects vesicle release and synaptic plasticity through the expression of synaptophysin.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Egor Dzyubenko, Wojciech Prazuch, Matthias Pillath-Eilers, Joanna Polanska, Dirk M. Hermann
Summary: The Astral software package is a novel tool for analyzing intercellular communication in astrocytic networks, without the need for assigning regions of interest. By using this tool, the network-wide quantification of Ca++ events and the analysis of their intercellular propagation can be achieved.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Steven A. Hill, Marissa Fu, A. Denise R. Garcia
Summary: Astrocytes are complex cells performing essential functions in the nervous system. The Sonic hedgehog (Shh) signaling pathway plays a crucial role in regulating the molecular identity and functional properties of astrocytes, and is active in specific subpopulations of these cells throughout the brain.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Clinical Neurology
Noemi Esteras, Olga Kopach, Marta Maiolino, Vincenzo Lariccia, Salvatore Amoroso, Seema Qamar, Selina Wray, Dmitri A. Rusakov, Morana Jaganjac, Andrey Y. Abramov
Summary: The study found that overproduction of mitochondrial reactive oxygen species (ROS) in 10+16 neurons alters the trafficking of specific glutamate receptor subunits, leading to impaired glutamatergic signaling, calcium overload, and excitotoxicity. Mitochondrial antioxidants can restore the altered response and prevent neuronal death. Additionally, extracellular 4R tau induces the same pathological response in healthy neurons, proposing a mechanism for disease propagation.
ALZHEIMERS & DEMENTIA
(2022)
Article
Biochemistry & Molecular Biology
Nafisa R. Komilova, Plamena R. Angelova, Alexey Berezhnov, Olga A. Stelmashchuk, Ulugbek Z. Mirkhodjaev, Henry Houlden, Alexander Gourine, Noemi Esteras, Andrey Y. Abramov
Summary: The study shows that acidification of the cytosol through compounds like lactate and pyruvate induces activation of mitophagy and autophagy in cells with PD mutations, protecting against cell death. Moreover, applying lactate to brain slices of WT and Pink1 KO mice also leads to a reduction in pH and increased mitophagy levels. This suggests that compounds which induce cytosolic acidification play a key role in activating protective mechanisms against neurodegeneration in PD.
Article
Cell Biology
Nuria Seto-Salvia, Noemi Esteras, Rohan de Silva, Eduardo de Pablo-Fernandez, Charles Arber, Christina E. Toomey, James M. Polke, Huw R. Morris, Jonathan D. Rohrer, Andrey Y. Abramov, Rickie Patani, Selina Wray, Thomas T. Warner
Summary: The intronic mutation in the microtubule-associated protein tau gene (MAPT) increases the expression of four-repeat (4R)-tau isoforms, leading to frontotemporal lobar degeneration (FTLD). Research on astrocytes from induced pluripotent stem cells of asymptomatic carriers with the mutation showed consistently elevated levels of 4R-tau in both astrocytes and neurons. This suggests a potential involvement of astrocytes in the pathogenic process of FTLD and indicates cell-type-specific regulation that could inform treatment strategies for pre-clinical tauopathies.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Mario Barilani, Christopher Lovejoy, Roberta Piras, Andrey Y. Abramov, Lorenza Lazzari, Plamena R. Angelova
Summary: The study found that aging in MSCs is associated with changes in mitochondrial metabolism, including a decrease in mitochondrial membrane potential, lower NADH levels, and higher mitochondrial DNA content. Despite higher ATP levels in aged cells, increased rates of mitophagy lead to decreased overall mitochondrial mass. Additionally, changes in mitochondrial metabolism in aged MSCs result in the overproduction of reactive oxygen species in mitochondria, which is compensated by higher levels of the endogenous antioxidant glutathione.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Irina N. Novikova, Elena V. Potapova, Viktor V. Dremin, Andrey V. Dunaev, Andrey Y. Abramov
Summary: Singlet oxygen, an electronically excited state of triplet oxygen, can be generated by various means. The selectivity of 1267 nm laser in producing singlet oxygen was confirmed in this study. Singlet oxygen was found to induce apoptosis in cancer B16 melanoma cells but not in control fibroblasts by opening mitochondrial permeability transition pore.
Article
Neurosciences
Minee L. Choi, Alexandre Chappard, Bhanu P. Singh, Catherine Maclachlan, Margarida Rodrigues, Evgenia Fedotova, Alexey Berezhnov, Suman De, Chris Peddie, Dilan Athauda, Gurvir S. Virdi, Weijia Zhang, James R. Evans, Anna Wernick, Zeinab Shadman Zanjani, Plamena R. Angelova, Noemi Esteras, Andrey Vinikurov, Katie Morris, Kiani Jeacock, Laura Tosatto, Daniel Little, Paul Gissen, David J. Clarke, Tilo Kunath, Lucy Collinson, David Klenerman, Andrey Y. Abramov, Mathew H. Horrocks, Sonia Gandhi
Summary: This study tracked the initial self-assembly, oligomerization and structural conversion of alpha-synuclein inside neurons. Early seeding events occur on mitochondrial membranes, where oligomerization induces mitochondrial dysfunction and neuronal loss.
NATURE NEUROSCIENCE
(2022)
Correction
Neurosciences
Minee L. Choi, Alexandre Chappard, Bhanu P. Singh, Catherine Maclachlan, Margarida Rodrigues, Evgeniya I. Fedotova, Alexey V. Berezhnov, Suman De, Christopher J. Peddie, Dilan Athauda, Gurvir S. Virdi, Weijia Zhang, James R. Evans, Anna I. Wernick, Zeinab Shadman Zanjani, Plamena R. Angelova, Noemi Esteras, Andrey Y. Vinokurov, Katie Morris, Kiani Jeacock, Laura Tosatto, Daniel Little, Paul Gissen, David J. Clarke, Tilo Kunath, Lucy Collinson, David Klenerman, Andrey Y. Abramov, Mathew H. Horrocks, Sonia Gandhi
NATURE NEUROSCIENCE
(2022)
Article
Neurosciences
Gurvir S. Virdi, Minee L. Choi, James R. Evans, Zhi Yao, Dilan Athauda, Stephanie Strohbuecker, Raja S. Nirujogi, Anna Wernick, Noelia Pelegrina-Hidalgo, Craig Leighton, Rebecca S. Saleeb, Olga Kopach, Haya Alrashidi, Daniela Melandri, Jimena Perez-Lloret, Plamena R. Angelova, Sergiy Sylantyev, Simon Eaton, Simon Heales, Dmitri A. Rusakov, Dario R. Alessi, Tilo Kunath, Mathew H. Horrocks, Andrey Y. Abramov, Rickie Patani, Sonia Gandhi
Summary: Using human-induced pluripotent stem cells, researchers have discovered that protein misfolding leading to intraneuronal oligomer formation is one of the earliest critical events in Parkinson's disease. This leads to cellular stress and ultimately neuronal death.
NPJ PARKINSONS DISEASE
(2022)
Article
Neurosciences
Andrey Y. Y. Vinokurov, Vladislav O. O. Soldatov, Evgenia S. S. Seregina, Angelina I. I. Dolgikh, Pavel A. A. Tagunov, Andrey V. V. Dunaev, Marina Y. Y. Skorkina, Alexey V. V. Deykin, Andrey Y. Y. Abramov
Summary: Alterations in function of HPRT lead to overproduction of uric acid and symptoms of LNS. HPRT1 deficiency inhibits mitochondrial respiration and increases ROS production, but does not induce oxidative stress or decrease the level of antioxidant glutathione.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Noemi Esteras, Thomas S. Blacker, Evgeny A. Zherebtsov, Olga A. Stelmashuk, Ying Zhang, W. Christian Wigley, Michael R. Duchen, Albena T. Dinkova-Kostova, Andrey Y. Abramov
Summary: The transcription factor Nrf2 and its repressor Keap1 play a crucial role in cell stress adaptation by regulating gene expression related to cellular detoxification, antioxidant defense, and energy metabolism. This study investigated the impact of Nrf2 on glucose distribution and the connection between NADH production in energy metabolism and NADPH homeostasis using glio-neuronal cultures. The findings showed that Nrf2 activation enhances glucose uptake in neurons and astrocytes, with prioritized consumption for mitochondria-related energy production rather than NADPH synthesis in the pentose phosphate pathway.
Article
Biochemistry & Molecular Biology
Plamena R. Angelova, Isabella Myers, Andrey Y. Abramov
Summary: A study found that carbon monoxide (CO) poisoning is a major cause of toxic mortality and morbidity. Reactive oxygen species were found to be generated in response to toxic doses of CO exposure, leading to lipid peroxidation and a decrease in GSH. Inhibition of different phases of reactive oxygen species generation protected cells against CO-induced oxidative stress and cell death, with the most significant effect observed during NADPH oxidase inhibition.
Article
Cell Biology
E. I. Fedotova, A. Y. Abramov, A. V. Berezhnov
Summary: Parkinson's disease is characterized by neuronal loss in the midbrain and dopamine-deficient states. It was hypothesized that dopamine may act as a glutamate antagonist and dopamine deficiency may increase glutamate-induced excitotoxicity. Through experiments on rat hippocampal primary culture, dopamine was found to reduce calcium response from NMDA receptors but not from AMPA and KA receptors or voltage-gated calcium channels. The protective effect of dopamine against glutamate toxicity was observed through the reduction of glutamate-induced mitochondrial depolarization and improvement of neuronal survival.
BIOCHEMISTRY MOSCOW SUPPLEMENT SERIES A-MEMBRANE AND CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sharadha Dayalan Naidu, Plamena R. Angelova, Elena V. Knatko, Chiara Leonardi, Miroslav Novak, Laureano de la Vega, Ian G. Ganley, Andrey Y. Abramov, Albena T. Dinkova-Kostova
Summary: Transcription factor Nrf2 plays a crucial role in maintaining cellular redox homeostasis and mitochondrial health in lung cancer cells with loss-of-function Keap1 mutations.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
E. Fedotova, A. Y. Abramov, A. Berezhnov
Summary: The study suggests that dopamine reduces the calcium response induced by NMDA receptor activation and improves neuronal survival in the presence of toxic levels of glutamate, indicating a protective role of dopamine against glutamate toxicity.
BIOLOGICHESKIE MEMBRANY
(2022)
Article
Gastroenterology & Hepatology
Plamena R. Angelova, Annarein J. C. Kerbert, Abeba Habtesion, Andrew Hall, Andrey Y. Abramov, Rajiv Jalan
Summary: This study revealed that hyperammonaemia, a common condition in patients with liver cirrhosis, severely impacts brain mitochondrial function, leading to neuronal injury and death. The findings suggest a novel mechanism of ammonia-induced brain injury in liver failure.
Article
Cell Biology
Dominic Tscherrig, Rajesh Bhardwaj, Daniel Biner, Jan Dernic, Daniela Ross-Kaschitza, Christine Peinelt, Matthias A. Hediger, Martin Lochner
Summary: Changes in Ca2+ levels regulate many physiological functions, and the endoplasmic reticulum is the major Ca2+ store in cells. Store-operated calcium entry (SOCE) is a refilling process that involves protein-protein interactions between Ca2+ sensing STIM in the ER and Orai proteins in the plasma membrane, forming selective Ca2+ channels. Abnormal SOCE is associated with diseases and cancers, making STIM and Orai important therapeutic targets. Novel GSK-7975A-based molecular probes have been developed for studying SOCE in different cells and settings.
Article
Cell Biology
Nicola Fameli, Cornelis van Breemen, Klaus Groschner
Summary: The study provides evidence for the importance of junctional membrane architecture in cellular function. Through modeling and prediction, it is shown that nano-scale membrane spacing plays a crucial role in junctional ER Ca2+ refilling and signaling efficiency. Additionally, interactions between Ca2+ and the phospholipid membrane surface are suggested to support interfacial Ca2+ transport and receptor targeting. This research introduces a new concept in pathophysiology.
Article
Cell Biology
Satomi Ohtsuka, Yumi Miyai, Hiroyuki Mima, Masaki Magari, Yoichi Chiba, Futoshi Suizu, Hiroyuki Sakagami, Masaki Ueno, Hiroshi Tokumitsu
Summary: This study characterized the splice variants of mouse CaMKKI3/2 and found that CaMKKI3-3 and I3-3x were functionally active and likely to be bona fide CaMKIV kinases involved in the regulation of spermiogenesis.
