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Cold Spring Harbor Perspectives in... Feb 2015Brain metabolism is characterized by fuel monodependence, high-energy expenditure, autonomy from the rest of body, local recycling, and marked division of labor between... (Review)
Review
Brain metabolism is characterized by fuel monodependence, high-energy expenditure, autonomy from the rest of body, local recycling, and marked division of labor between cell types. Although neurons spend most of the brain's energy on signaling, astrocytes bear the brunt of the metabolic load, controlling the composition of the interstitial fluid, supplying neurons with energy substrates and precursors for biosynthesis, and recycling neurotransmitters, oxidized scavengers, and other waste products. Outstanding questions in this field are the role of oligodendrocytes, the metabolic behavior of the different subtypes of astrocytes during development and disease, and the emerging notion that metabolism may participate directly in information processing.
Topics: Astrocytes; Brain; Energy Metabolism; Metabolic Networks and Pathways; Models, Biological
PubMed: 25680832
DOI: 10.1101/cshperspect.a020396 -
Molecular Psychiatry Jan 2022Drug addiction remains a key biomedical challenge facing current neuroscience research. In addition to neural mechanisms, the focus of the vast majority of studies to... (Review)
Review
Drug addiction remains a key biomedical challenge facing current neuroscience research. In addition to neural mechanisms, the focus of the vast majority of studies to date, astrocytes have been increasingly recognized as an "accomplice." According to the tripartite synapse model, astrocytes critically regulate nearby pre- and postsynaptic neuronal substrates to craft experience-dependent synaptic plasticity, including synapse formation and elimination. Astrocytes within brain regions that are implicated in drug addiction exhibit dynamic changes in activity upon exposure to cocaine and subsequently undergo adaptive changes themselves during chronic drug exposure. Recent results have identified several key astrocytic signaling pathways that are involved in cocaine-induced synaptic and circuit adaptations. In this review, we provide a brief overview of the role of astrocytes in regulating synaptic transmission and neuronal function, and discuss how cocaine influences these astrocyte-mediated mechanisms to induce persistent synaptic and circuit alterations that promote cocaine seeking and relapse. We also consider the therapeutic potential of targeting astrocytic substrates to ameliorate drug-induced neuroplasticity for behavioral benefits. While primarily focusing on cocaine-induced astrocytic responses, we also include brief discussion of other drugs of abuse where data are available.
Topics: Astrocytes; Cocaine-Related Disorders; Humans; Neuronal Plasticity; Synapses; Synaptic Transmission
PubMed: 33837268
DOI: 10.1038/s41380-021-01080-7 -
Progress in Neurobiology Mar 2019Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation... (Review)
Review
Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their transition towards reactive astrocytes to their ability to undergo reprogramming, thereby revealing their potential to retain latent features of neural progenitor cells. We propose that the mechanisms underlying reactive astrogliosis or astrocyte reprogramming provide an opportunity for initiating neuronal regeneration, a process that is notably reduced in the mammalian nervous system throughout evolution. Conversely, this plasticity may also affect normal astrocytic functions resulting in pathologies ranging from neurodevelopmental disorders to neurodegenerative diseases and brain tumors. We postulate that epigenetic mechanisms linking extrinsic cues and intrinsic transcriptional programs are key factors to maintain astrocyte identity and function, and critically, to control the balance of regenerative and degenerative activity. Here, we will review the main evidences supporting this concept. We propose that unravelling the epigenetic and transcriptional mechanisms underlying the acquisition of astrocyte identity and plasticity, as well as understanding how these processes are modulated by the local microenvironment under specific threatening or pathological conditions, may pave the way to new therapeutic avenues for several neurological disorders including neurodegenerative diseases and brain tumors of astrocytic lineage.
Topics: Animals; Astrocytes; Cell Differentiation; Cellular Reprogramming; Epigenesis, Genetic; Humans; Neurogenesis; Transcription, Genetic
PubMed: 30599178
DOI: 10.1016/j.pneurobio.2018.12.007 -
Current Opinion in Neurobiology Jun 2015Astrocytes are highly ramified glial cells found throughout the central nervous system (CNS). They express a variety of neurotransmitter receptors that can induce... (Review)
Review
Astrocytes are highly ramified glial cells found throughout the central nervous system (CNS). They express a variety of neurotransmitter receptors that can induce widespread chemical excitation, placing these cells in an optimal position to exert global effects on brain physiology. However, the activity patterns of only a small fraction of astrocytes have been examined and techniques to manipulate their behavior are limited. As a result, little is known about how astrocytes modulate CNS function on synaptic, microcircuit, or systems levels. Here, we review current and emerging approaches for visualizing and manipulating astrocyte activity in vivo. Deciphering how astrocyte network activity is controlled in different physiological and pathological contexts is crucial for defining their roles in the healthy and diseased CNS.
Topics: Animals; Astrocytes; Central Nervous System; Humans; Nerve Net; Signal Transduction
PubMed: 25665733
DOI: 10.1016/j.conb.2015.01.015 -
Brain Pathology (Zurich, Switzerland) May 2018Leukodystrophies are genetically determined disorders due to defects in any structural components of the brain white matter. This mini-symposium presents a selection of...
Leukodystrophies are genetically determined disorders due to defects in any structural components of the brain white matter. This mini-symposium presents a selection of leukodystrophies due to astrocytic dysfunction, the astrocytopathies. Examples are provided of astrocytopathies due to defects in astrocyte-specific proteins and in which astrocytes play a major role in the pathophysiology. Knowledge on the disease mechanisms underlying these leukodystrophies also provides information how loss of physiologic functions and gain of detrimental functions in astrocytes leads to degeneration of the white matter.
Topics: Animals; Astrocytes; Humans; Leukoencephalopathies
PubMed: 29740940
DOI: 10.1111/bpa.12607 -
Communications Biology May 2021Aggregation and self-sorting of cells in three dimensional cultures have been described for non-neuronal cells. Despite increased interest in engineered neural tissues...
Aggregation and self-sorting of cells in three dimensional cultures have been described for non-neuronal cells. Despite increased interest in engineered neural tissues for treating brain injury or for modeling neurological disorders in vitro, little data is available on collective cell movements in neuronal aggregates. Migration and sorting of cells may alter these constructs' morphology and, therefore, the function of their neural circuitry. In this work, linear, adhered rat and human 3D neuronal-astrocyte cultures were developed to enable the study of aggregation and sorting of these cells. An in silico model of the contraction, clustering, and cell sorting in the 3D cultures was also developed. Experiments and computational modeling showed that aggregation was mainly a neuron mediated process, and formation of astrocyte-rich sheaths in 3D cultures depended on differential attraction between neurons and astrocytes. In silico model predicted formation of self-assembled neuronal layers in disk-shaped 3D cultures. Neuronal activity patterns were found to correlate with local morphological differences. This model of neuronal and astrocyte aggregation and sorting may benefit future design of neuronal constructs.
Topics: Animals; Astrocytes; Cell Movement; Cell Survival; Coculture Techniques; Neurons; Rats; Rats, Sprague-Dawley
PubMed: 34002005
DOI: 10.1038/s42003-021-02104-2 -
Advances in Neurobiology 2021The role of astrocytes in the nervous system pathology was early on embraced by neuroscientists at end of the nineteenth and the beginning of the twentieth century, only...
The role of astrocytes in the nervous system pathology was early on embraced by neuroscientists at end of the nineteenth and the beginning of the twentieth century, only to be pushed aside by neurone-centric dogmas during most of the twentieth century. However, the last decade of the twentieth century and the twenty-first century have brought the astroglial "renaissance", which has put astroglial cells as key players in pathophysiology of most if not all disorders of the nervous system and has regarded astroglia as a fertile ground for therapeutic intervention.Astrocytic contribution to neuropathology can be primary, whereby cell-autonomous changes, such as mutations in gene encoding for glial fibrillary acidic protein, can drive the pathologic progression, in this example, Alexander disease. They can also be secondary, when astrocytes respond to a variety of insults to the nervous tissue. Regardless of their origin, being cell-autonomous or not, changes in astroglia that occur in pathology, that is, astrogliopathology, can be contemporary and arbitrary classified into four forms: (i) reactive astrogliosis, (ii) astrocytic atrophy with loss of function, (iii) pathological remodelling of astrocytes and (iv) astrodegeneration morphologically manifested as clasmatodendrosis. Inevitably, as with any other classification, this classification of astrogliopathology awaits its revision that shall be rooted in new discoveries and concepts.
Topics: Alexander Disease; Astrocytes; Atrophy; Gliosis; Humans
PubMed: 34888830
DOI: 10.1007/978-3-030-77375-5_3 -
Glia Aug 2022Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections... (Review)
Review
Brain circuits undergo substantial structural changes during development, driven by the formation, stabilization, and elimination of synapses. Synaptic connections continue to undergo experience-dependent structural rearrangements throughout life, which are postulated to underlie learning and memory. Astrocytes, a major glial cell type in the brain, are physically in contact with synaptic circuits through their structural ensheathment of synapses. Astrocytes strongly contribute to the remodeling of synaptic structures in healthy and diseased central nervous systems by regulating synaptic connectivity and behaviors. However, whether structural plasticity of astrocytes is involved in their critical functions at the synapse is unknown. This review will discuss the emerging evidence linking astrocytic structural plasticity to synaptic circuit remodeling and regulation of behaviors. Moreover, we will survey possible molecular and cellular mechanisms regulating the structural plasticity of astrocytes and their non-cell-autonomous effects on neuronal plasticity. Finally, we will discuss how astrocyte morphological changes in different physiological states and disease conditions contribute to neuronal circuit function and dysfunction.
Topics: Astrocytes; Brain; Neuronal Plasticity; Neurons; Synapses
PubMed: 35535566
DOI: 10.1002/glia.24191 -
Neural Plasticity 2014The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the... (Review)
Review
The function and efficacy of synaptic transmission are determined not only by the composition and activity of pre- and postsynaptic components but also by the environment in which a synapse is embedded. Glial cells constitute an important part of this environment and participate in several aspects of synaptic functions. Among the glial cell family, the roles played by astrocytes at the synaptic level are particularly important, ranging from the trophic support to the fine-tuning of transmission. Astrocytic structures are frequently observed in close association with glutamatergic synapses, providing a morphological entity for bidirectional interactions with synapses. Experimental evidence indicates that astrocytes sense neuronal activity by elevating their intracellular calcium in response to neurotransmitters and may communicate with neurons. The precise role of astrocytes in regulating synaptic properties, function, and plasticity remains however a subject of intense debate and many aspects of their interactions with neurons remain to be investigated. A particularly intriguing aspect is their ability to rapidly restructure their processes and modify their coverage of the synaptic elements. The present review summarizes some of these findings with a particular focus on the mechanisms driving this form of structural plasticity and its possible impact on synaptic structure and function.
Topics: Animals; Astrocytes; Humans; Neural Pathways; Neuronal Plasticity; Rats; Synapses
PubMed: 24511394
DOI: 10.1155/2014/232105 -
Glia Jan 2023The study of the astrocytic contribution to brain functions has been growing in popularity in the neuroscience field. In the last years, and especially since the... (Review)
Review
The study of the astrocytic contribution to brain functions has been growing in popularity in the neuroscience field. In the last years, and especially since the demonstration of the involvement of astrocytes in synaptic functions, the astrocyte field has revealed multiple functions of these cells that seemed inconceivable not long ago. In parallel, cannabinoid investigation has also identified different ways by which cannabinoids are able to interact with these cells, modify their functions, alter their communication with neurons and impact behavior. In this review, we will describe the expression of different endocannabinoid system members in astrocytes. Moreover, we will relate the latest findings regarding cannabinoid modulation of some of the most relevant astroglial functions, namely calcium (Ca ) dynamics, gliotransmission, metabolism, and inflammation.
Topics: Astrocytes; Endocannabinoids; Neurons; Calcium; Cannabinoids; Calcium Signaling
PubMed: 35822691
DOI: 10.1002/glia.24246