Mutations in the transcriptional regulator MeCP2 severely impact key cellular and molecular signatures of human astrocytes during maturation DOI Creative Commons
Jialin Sun,

Sivan Osenberg,

Austin Irwin

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111942 - 111942

Published: Jan. 1, 2023

Mutations in the MECP2 gene underlie a spectrum of neurodevelopmental disorders, most commonly Rett syndrome (RTT). We ask whether mutations interfere with human astrocyte developmental maturation, thereby affecting their ability to support neurons. Using human-based models, we show that RTT-causing greatly impact key role astrocytes regulating overall brain bioenergetics and these metabolic aberrations are likely mediated by dysfunctional mitochondria. During post-natal rely on neurons induce complex stellate morphology transcriptional changes. While cause cell-intrinsic landscape, surprisingly, they do not affect neuron-induced expression. Notably, however, unable develop mature due cell- non-cell-autonomous caused mutations. Thus, critically cellular molecular features and, hence, interact structural functional maturation

Language: Английский

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury DOI Creative Commons
Michelle A. Bylicky, Gregory P. Mueller, Regina M. Day

et al.

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

Astrocytes, once believed to serve only as "glue" for the structural support of neurons, have been demonstrated critical functions maintenance and protection especially under conditions acute or chronic injury. There are at least seven distinct mechanisms by which astrocytes protect neurons from damage; these (1) against glutamate toxicity, (2) redox stress, (3) mediation mitochondrial repair mechanisms, (4) glucose-induced metabolic (5) iron (6) modulation immune response in brain, (7) tissue homeostasis presence DNA damage. Astrocytes through specialized responses stress toxic conditions. The detoxifying activities essential microenvironment surrounding whole homeostasis. Improved understanding brain could lead development novel targets neuroprotective strategies.

Language: Английский

Citations

138
Astroglial glutamate transporters coordinate excitatory signaling and brain energetics DOI
Michael B. Robinson, Joshua G. Jackson

Neurochemistry International, Journal Year: 2016, Volume and Issue: 98, P. 56 - 71

Published: March 21, 2016

Language: Английский

Citations

133
Regulation of mitochondrial dynamics in astrocytes: Mechanisms, consequences, and unknowns DOI
Joshua G. Jackson, Michael B. Robinson

Glia, Journal Year: 2017, Volume and Issue: 66(6), P. 1213 - 1234

Published: Nov. 3, 2017

Abstract Astrocytes are the major glial cell in central nervous system. These polarized cells possess numerous processes that ensheath vasculature and contact synapses. play important roles synaptic signaling, neurotransmitter synthesis recycling, control of nutrient uptake, local blood flow. Many these depend on metabolism and/or energy utilization. While astrocytes respond to increases neuronal activity metabolic demand by upregulating glycolysis glycogenolysis, also significant capacity for oxidative (mitochondrial) metabolism. Mitochondria mediate supply metabolism, cellular survival, ionic homeostasis, proliferation. organelles dynamic structures undergoing extensive fission fusion, directed movement along cytoskeletal tracts, degradation. many mechanisms underlying dynamics their physiologic have been characterized neurons other cells, mitochondrial physiology is less well understood. Recent work from several laboratories has demonstrated mitochondria present within fine astrocytes, regulated, they contribute Ca 2+ signaling astrocyte. They likely a role ATP production particularly glutamate. Here we will review findings describing mechanism which regulated how might influence astrocyte brain draw parallels neurons. Additionally, new analyses size, distribution, performed using vivo 2‐photon microscopy.

Language: Английский

Citations

131
Astrocytes and microglia: Models and tools DOI Creative Commons
Kevin A. Guttenplan, Shane A. Liddelow

The Journal of Experimental Medicine, Journal Year: 2018, Volume and Issue: 216(1), P. 71 - 83

Published: Dec. 12, 2018

Glial cells serve as fundamental regulators of the central nervous system in development, homeostasis, and disease. Discoveries into function these have fueled excitement glial research, with enthusiastic researchers addressing questions about biology producing new scientific tools for community. Here, we outline pros cons vivo vitro techniques to study astrocytes microglia goal helping quickly identify best approach a given research question context biology. It is truly great time be biologist.

Language: Английский

Citations

126
Astrocyte alterations in neurodegenerative pathologies and their modeling in human induced pluripotent stem cell platforms DOI Creative Commons

Minna Oksanen,

Šárka Lehtonen, Merja Jaronen

et al.

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(14), P. 2739 - 2760

Published: April 23, 2019

Astrocytes are the most abundant cell type in brain. They were long considered only as passive support for neuronal cells. However, recent data have revealed many active roles these cells both maintenance of normal physiological homeostasis brain well neurodegeneration and disease. Moreover, human astrocytes been found to be much more complex than their rodent counterparts, date, known actively participate a multitude processes such neurotransmitter uptake recycling, gliotransmitter release, neuroenergetics, inflammation, modulation synaptic activity, ionic balance, blood–brain barrier, other crucial functions This review focuses on role neurodegenerative disease potential novel stem cell-based platforms modeling astrocytic health

Language: Английский

Citations

121
The Energy Homeostasis Principle: Neuronal Energy Regulation Drives Local Network Dynamics Generating Behavior DOI Creative Commons
Rodrigo C. Vergara, Alfonso Jaramillo, Alejandro Luarte

et al.

Frontiers in Computational Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: July 23, 2019

A major goal of neuroscience is understanding how neurons arrange themselves into neural networks that result in behavior. Most theoretical and experimental efforts have focused on a top-down approach which seeks to identify neuronal correlates behaviors. This has been accomplished by effectively mapping specific behaviors distinct patterns, or creating computational models produce desired behavioral outcome. Nonetheless, these approaches only implicitly considered the fact tissue, like any other physical system, subjected several restrictions boundaries operations. Here, we proposed new, bottom-up conceptual paradigm: The Energy Homeostasis Principle, where balance between energy income, expenditure, availability are key parameters determining dynamics phenomena found from molecular levels. Neurons display high consumption relative cells, with metabolic brain representing 20% whole-body oxygen uptake, contrasting this organ 2% body weight. Also, specialized surrounding tissue providing necessary which, case brain, provided astrocytes. Moreover, unlike cell types demands such as muscle strict aerobic metabolism. These facts indicate highly sensitive limitations, Gibb's free dictating direction all cellular processes. From activity, largest energy, far, expended action potentials post-synaptic potentials; therefore, plasticity can be reinterpreted terms their context. Consequently, neurons, through synapses, impose over close loop-manner, modulating local circuits. Subsequently, end up impacting homeostatic mechanisms networks. Furthermore, management also emerges population property, most expenses triggered sensory modulatory inputs. Local may sufficient explain emergence behavior, enabling assessment properties arise circuits how. Essentially, proposal Principle readily testable for simple

Language: Английский

Citations

118
Mitochondrial Metabolism in Astrocytes Regulates Brain Bioenergetics, Neurotransmission and Redox Balance DOI Creative Commons

Jordan Rose,

Christian Brian,

Aglaia Pappa

et al.

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Nov. 5, 2020

In the brain, mitochondrial metabolism has been largely associated with energy production, and its dysfunction is linked to neuronal cell loss. However, functional role of mitochondria in glial cells poorly studied. Recent reports have demonstrated unequivocally that astrocytes do not require meet their bioenergetics demands. Then, question remaining is, what astrocytes? this work, we review current evidence demonstrating central carbon regulates overall brain bioenergetics, neurotransmitter homeostasis redox balance. Emphasis placed detailing source utilization (glucose fatty acids), anaplerotic inputs cataplerotic outputs, as well shuttles neurons, which highlight metabolic specialization astrocytic relevance function.

Language: Английский

Citations

118
The Role of Lactate-Mediated Metabolic Coupling between Astrocytes and Neurons in Long-Term Memory Formation DOI Creative Commons

Michael Q. Steinman,

Virginia Gao, Cristina M. Alberini

et al.

Frontiers in Integrative Neuroscience, Journal Year: 2016, Volume and Issue: 10

Published: March 3, 2016

Long-term memory formation, the ability to retain information over time about an experience, is a complex function that affects multiple behaviors, and integral part of individual's identity. In last 50 years many scientists have focused their work on understanding biological mechanisms underlying formation processing. Molecular studies three decades mostly investigated, or given attention to, neuronal mechanisms. However, brain composed different cell types that, by concerted actions, cooperate mediate functions. Here we consider some new insights emerged from recent implicating astrocytic glycogen glucose metabolisms, particularly coupling functions via lactate, as essential mechanism for long-term formation.

Language: Английский

Citations

112
Mechanisms for the maintenance and regulation of axonal energy supply DOI
Kelly A. Chamberlain, Zu‐Hang Sheng

Journal of Neuroscience Research, Journal Year: 2019, Volume and Issue: 97(8), P. 897 - 913

Published: March 18, 2019

The unique polarization and high-energy demand of neurons necessitates specialized mechanisms to maintain energy homeostasis throughout the cell, particularly in distal axon. Mitochondria play a key role meeting axonal by generating adenosine triphosphate through oxidative phosphorylation. Recent evidence demonstrates how mitochondrial trafficking anchoring are coordinated sense respond altered requirements. If when these impacted pathological conditions, such as injury neurodegenerative disease, is an emerging research frontier. also suggests that may be supplemented local glial cells, including astrocytes oligodendrocytes. In this review, we provide updated discussion phosphorylation, aerobic glycolysis, oligodendrocyte-derived metabolic support contribute maintenance homeostasis.

Language: Английский

Citations

95
Defects in Bioenergetic Coupling in Schizophrenia DOI
Courtney R. Sullivan, Sinead M. O’Donovan, Robert E. McCullumsmith

et al.

Biological Psychiatry, Journal Year: 2017, Volume and Issue: 83(9), P. 739 - 750

Published: Oct. 24, 2017

Language: Английский

Citations

93