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Renjini Ramadasan-Nair, Jessica Hui, Leslie S Itsara, Philip G Morgan, Margaret M Sedensky
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: In mice, restriction of loss of the mitochondrial complex I gene Ndufs4 to glutamatergic neurons confers a profound hypersensitivity to volatile anesthetics.Astrocytes are crucial to glutamatergic synapse functioning during excitatory transmission. WHAT THIS ARTICLE TELLS US THAT IS NEW: In a tamoxifen-activated astrocyte-specific Ndufs4(KO) mouse, the induction EC50s for tail clamp in both isoflurane and halothane were similar between the control and astrocyte-specific Ndufs4(KO) mice at 3 weeks after 4-hydroxy tamoxifen injection...
January 28, 2019: Anesthesiology
Gerald A Dienel
Glycogen levels in resting brain and its utilization rates during brain activation are high, but the functions fulfilled by glycogenolysis in living brain are poorly understood. Studies in cultured astrocytes have identified glycogen as the preferred fuel to provide ATP for Na+ ,K+ -ATPase for the uptake of extracellular K+ and for Ca2+ -ATPase to pump Ca2+ into the endoplasmic reticulum. Studies in astrocyte-neuron co-cultures led to the suggestion that glycogen-derived lactate is shuttled to neurons as oxidative fuel to support glutamatergic neurotransmission...
January 22, 2019: Journal of Neuroscience Research
Alexey Semyanov
Ca2+ influx through an astrocyte plasma membrane is mediated by ionotropic receptors and Ca2+ channels according the electrochemical gradient. These conductances allow astrocytes to sense the levels of neuronal activity and environmental changes. Na+ /Ca2+ exchanger (NCX) removes elevated Ca2+ from the cell but can reverse and bring Ca2+ in. Ca2+ entry through the plasma membrane produces local Ca2+ elevations that can be further amplified by Ca2+ induced activation of inositol-3-phosphate (IP3 ) receptors and subsequent Ca2+ release from intracellular Ca2+ stores...
December 17, 2018: Cell Calcium
Michael Barros, Subhrakanti Dey
Synaptic plasticity depends on the gliotransmitters' concentration in the synaptic channel. And, an abnormal concentration of gliotransmitters is linked to neurodegenerative diseases, including Alzheimer's, Parkinson's, and epilepsy. In this paper, a theoretical investigation of the cause of the abnormal concentration of gliotransmitters and how to achieve its control is presented through a Ca2+-signalling-based molecular communications framework. A feed-forward and feedback control technique is used to manipulate IP3 values to stabilise the concentration of Ca2+ inside the astrocytes...
December 18, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Verónica Abudara, Mauricio A Retamal, Rodrigo Del Rio, Juan A Orellana
The classical view of synapses as the functional contact between presynaptic and postsynaptic neurons has been challenged in recent years by the emerging regulatory role of glial cells. Astrocytes, traditionally considered merely supportive elements are now recognized as active modulators of synaptic transmission and plasticity at the now so-called "tripartite synapse." In addition, an increasing body of evidence indicates that beyond immune functions microglia also participate in various processes aimed to shape synaptic plasticity...
2018: Frontiers in Molecular Neuroscience
Caitlin A Durkee, Alfonso Araque
Astrocytes are emerging as important players in synaptic function, and, consequently, on brain function and animal behavior. According to the Tripartite Synapse concept, astrocytes are integral elements involved in synaptic function. They establish bidirectional communication with neurons, whereby they respond to synaptically released neurotransmitters and, in turn, release gliotransmitters that influence neuronal and synaptic activity. Accumulating evidence is revealing that the mechanisms and functional consequences of astrocyte-neuron signaling are more complex than originally thought...
November 17, 2018: Neuroscience
Xi Lan, Xiaoning Han, Xi Liu, Jian Wang
Inflammatory responses occur rapidly after intracerebral hemorrhage and participate in both short-term toxicity and long-term recovery. Microglia/macrophages react to hemorrhagic injury and exhibit dynamic phenotypes and phagocytic capability. Astrocytes secrete cytokines, chemokines, and gliotransmitters that can regulate neuroinflammation. In addition, infiltrating neutrophils and T-lymphocytes modulate immunoreactions, which further cross-talk with microglia/macrophages. Thus, the search for effective immunotherapy to target specific cell type-mediated inflammation might represent a new direction for intracerebral hemorrhage treatment, separate from traditional anti-inflammatory drug discovery...
October 22, 2018: Journal of Cerebral Blood Flow and Metabolism
Han Luo, Peng-Fei Wu, Qian-Qian Han, Yu Cao, Si-Long Deng, Ji Wang, Qiao Deng, Fang Wang, Jian-Guo Chen
AIMS: Astrocytes have been revealed as a controller of synaptic plasticity and memory via releasing gliotransmitters. Our recent findings showed that reactive sulfur species (RSS), including hydrogen sulfide (H2 S) and polysulfide (H2 Sn ), regulated the availability of d-serine, which is a well-known gliotransmitter that is involved in synaptic plasticity. An interesting question is whether RSS, which are small molecules, can function as direct gliotransmitters to integrate astrocyte-neuron interactions throughout the memory process...
October 12, 2018: Antioxidants & Redox Signaling
Marta Gómez-Gonzalo, Tamara Zehnder, Linda Maria Requie, Paola Bezzi, Giorgio Carmignoto
The gliotransmitter glutamate in different brain regions modulates neuronal excitability and synaptic transmission through a variety of mechanisms. Among the hallmarks of astrocytic glutamate release are the slow depolarizing inward currents (SICs) in neurons mediated by N-methyl-d-aspartate receptor activation. Different stimuli that evoke Ca2+ elevations in astrocytes induce neuronal SICs suggesting a Ca2+ -dependent exocytotic glutamate release mechanism of SIC generation. To gain new insights into this mechanism, we investigated the relationship between astrocytic Ca2+ elevations and neuronal SICs in mouse hippocampal slice preparations...
October 2018: Glia
Mehdi Borjkhani, Fariba Bahrami, Mahyar Janahmadi
There are several experimental studies which suggest opioids consumption forms pathological memories in different brain regions. For example it has been empirically demonstrated that the theta rhythm which appears during chronic opioid consumption is correlated with the addiction memory formation. In this paper, we present a minimal computational model that shows how opioids can change firing patterns of the neurons during acute and chronic opioid consumption and also during withdrawal periods. The model consists of a pre- and post-synaptic neuronal circuits and the astrocyte that monitors the synapses...
2018: Frontiers in Computational Neuroscience
Karen M Crosby, Ciaran Murphy-Royal, Sarah A Wilson, Grant R Gordon, Jaideep S Bains, Quentin J Pittman
Whether synapses in appetite-regulatory brain regions undergo long-term changes in strength in response to satiety peptides is poorly understood. Here we show that following bursts of afferent activity, the neuromodulator and satiety peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long-term depression to long-term potentiation (LTP). This LTP requires the activation of both type 2 CCK receptors and group 5 metabotropic glutamate receptors, resulting in a rise in astrocytic intracellular calcium and subsequent ATP release...
October 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Rasmus Kordt Christensen, Rodolfo Delgado-Lezama, Raúl E Russo, Barbara Lykke Lind, Emanuel Loeza Alcocer, Martin Fredensborg Rath, Gabriela Fabbiani, Nicole Schmitt, Martin Lauritzen, Anders Victor Petersen, Eva Meier Carlsen, Jean-François Perrier
KEY POINTS: GABA is an essential molecule for sensory information processing. It is usually assumed to be released by neurons. Here we show that in the dorsal horn of the spinal cord, astrocytes respond to glutamate by releasing GABA. Our findings suggest a novel role for astrocytes in somatosensory information processing. ABSTRACT: Astrocytes participate in neuronal signalling by releasing gliotransmitters in response to neurotransmitters. We investigated if astrocytes from the dorsal horn of the spinal cord of adult red-eared turtles (Trachemys scripta elegans) release GABA in response to glutamatergic receptor activation...
October 2018: Journal of Physiology
Ulyana Lalo, Alexander Bogdanov, Yuriy Pankratov
Activity-dependent regulation of synaptic plasticity, or metaplasticity, plays a key role in the adaptation of neuronal networks to physiological and biochemical changes in aging brain. There is a growing evidence that experience-related alterations in the mechanisms of synaptic plasticity can underlie beneficial effects of physical exercise and caloric restriction (CR) on brain health and cognition. Astrocytes, which form neuro-vascular interface and can modulate synaptic plasticity by release of gliotransmitters, attract an increasing attention as important element of brain metaplasticity...
2018: Frontiers in Molecular Neuroscience
David Forsberg, Eric Herlenius
The role of astrocytes in the modulation of breathing has emerged. Within the two major respiratory control centers, the inspiration generating preBötzinger Complex and the chemosensitive parafacial respiratory group/retrotrapezoid nucleus, rhythmically active astrocytes have been discovered. These are connected in glial subnetworks that intermingle with the neuronal network. Furthermore, astrocytes modify overall respiratory network behavior through gliotransmitter release, especially during hypoxic and hypercapnic stress...
June 30, 2018: Respiratory Physiology & Neurobiology
Nolwenn Pasquet, Sara Douceau, Mickael Naveau, Flavie Lesept, Morgane Louessard, Laurent Lebouvier, Yannick Hommet, Denis Vivien, Isabelle Bardou
Modifications of neuronal migration during development, including processes that control cortical lamination are associated with functional deficits at adult stage. Here, we report for the first time that the lack of the serine protease tissue-type Plasminogen Activator (tPA), previously characterized as a neuromodulator and a gliotransmitter, leads to an altered cortical lamination in adult. This results in a neuronal migration defect of tPA deficient neurons which are stopped in the intermediate zone at E16...
June 6, 2018: Cerebral Cortex
Changsi Cai, Jonas C Fordsmann, Sofie H Jensen, Bodil Gesslein, Micael Lønstrup, Bjørn O Hald, Stefan A Zambach, Birger Brodin, Martin J Lauritzen
Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5-20 µm/s...
June 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Anikó Kárpáti, Takeo Yoshikawa, Tadaho Nakamura, Tomomitsu Iida, Takuro Matsuzawa, Haruna Kitano, Ryuichi Harada, Kazuhiko Yanai
Astrocytes play key roles in regulating brain homeostasis and neuronal activity. This is, in part, accomplished by the ability of neurotransmitters in the synaptic cleft to bind astrocyte membrane receptors, activating signalling cascades that regulate concentration of intracellular Ca2+ ([Ca2+ ]i ) and gliotransmitter release, including ATP and glutamate. Gliotransmitters contribute to dendrite formation and synaptic plasticity, and in some cases, exacerbate neurodegeneration. The neurotransmitter histamine participates in several physiological processes, such as the sleep-wake cycle and learning and memory...
June 2018: Journal of Pharmacological Sciences
Andrei D Ivanov, Jean-Pierre Mothet
d-Serine is now recognized as the main co-agonist for NMDA receptors. For years it was thought to be exclusively produced by astrocytes and was thus viewed as the archetype of gliotransmitters. Recent research have challenged this long cherished and appealing view by showing that in physiological conditions d-erine would rather originate from neurons but not from glia. In the present review and in the light of the emerging serine shuttle model, we ambition to offer a new reading direction of the glia-neuron cross-talk in shaping the metabolism and the functions of d-serine in cerebral communication in normal and pathological conditions by re-interpretating some seminal findings...
May 28, 2018: Neuroscience Letters
Mai Takizawa, Kazuki Harada, Kazuaki Nakamura, Takashi Tsuboi
Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca2+ concentration ([Ca2+ ]i ) and releasing chemical molecules called gliotransmitters. Recently discovered Ca2+ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca2+ ]i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca2+ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown...
July 2, 2018: Biochemical and Biophysical Research Communications
Gerwyn Morris, Brendon Stubbs, Cristiano A Köhler, Ken Walder, Anastasiya Slyepchenko, Michael Berk, André F Carvalho
Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders...
October 2018: Sleep Medicine Reviews
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