The astrocyte biochemistry

Souza, Débora Guerini de; Almeida, Roberto Farina de; Souza, Diogo Onofre Gomes de; Zimmer, Eduardo R.

doi:10.1016/j.semcdb.2019.04.002

Cited by 48 publications

(44 citation statements)

References 131 publications

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“…If this intercellular compartmentalization between neurons and astroglia operates in the resting and/or activated brain, the measured CMR glc would reflect mainly astroglial glucose utilization, since neurons utilize lactate derived from astroglia. This hypothetical model, termed the “astrocyte‐neuron lactate shuttle hypothesis (ANLSH)”, was originally proposed by Pellerin and Magistretti in 1994 based on data obtained using cultured cells and was supported by our findings but has remained controversial for more than a quarter of a century …”

Section: Glucose and Lacatesupporting

confidence: 70%

“…Co‐transported Na + and glutamate increase the intracellular concentration of Na + ([Na + ] i ), leading to the activation of Na + ,K + ‐ATPase; this, in turn, accelerates ATP production in astroglia. Whether ATP production in astroglia is dependent on glycolysis or the mitochondrial oxidative metabolism of glucose continues to be a matter of long‐lasting debate . An in vitro experiment showed that glutamate stimulation does, indeed, increase glucose consumption and lactate production by astroglia (i.e., aerobic glycolysis) .…”

Section: Glucose and Lacatementioning

confidence: 99%

“…Irrespective of accumulating evidence supporting the ANLSH, the fate of lactate, if it is really produced by astroglia via a glutamate signal from activated neurons, has remained a matter of controversy for more than 25 years . The original ANLSH followed by numerous reports proposed that activated neurons consume lactate produced by astroglia .…”

Section: Glucose and Lacatementioning

confidence: 99%

“…This hypothetical model, termed the "astrocyte-neuron lactate shuttle hypothesis (ANLSH)", was originally proposed by Pellerin and Magistretti in 1994 based on data obtained using cultured cells 66 and was supported by our findings 67,68 but has remained controversial for more than a quarter of a century. 69,70 metabolism is inhibited, while neurons cannot. 72 Glucose uptake or utilization (phosphorylation by hexokinase [HK]) can be quantified using cultured astroglia and neurons in vitro and in vivo using modern molecular techniques, 73 while the quantitation of oxygen consumption is more difficult.…”

Section: Glucose Utilization By Astrogliamentioning

confidence: 99%

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Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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Astroglia or astrocytes, the most abundant cells in the brain, are interposed between neuronal synapses and microvasculature in the brain gray matter. They play a pivotal role in brain metabolism as well as in the regulation of cerebral blood flow, taking advantage of their unique anatomical location. In particular, the astroglial cellular metabolic compartment exerts supportive roles in dedicating neurons to the generation of action potentials and protects them against oxidative stress associated with their high energy consumption. An impairment of normal astroglial function, therefore, can lead to numerous neurological disorders including stroke, neurodegenerative diseases, and neuroimmunological diseases, in which metabolic derangements accelerate neuronal damage. The neurovascular unit (NVU), the major components of which include neurons, microvessels, and astroglia, is a conceptual framework that was originally used to better understand the pathophysiology of cerebral ischemia. At present, the NVU is a tool for understanding normal brain physiology as well as the pathophysiology of numerous neurological disorders. The metabolic responses of astroglia in the NVU can be either protective or deleterious. This review focuses on three major metabolic compartments: (i) glucose and lactate; (ii) fatty acid and ketone bodies; and (iii) D‐ and L‐serine. Both the beneficial and the detrimental roles of compartmentalization between neurons and astroglia will be discussed. A better understanding of the astroglial metabolic response in the NVU is expected to lead to the development of novel therapeutic strategies for diverse neurological diseases.

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Section: Glucose and Lacatesupporting

confidence: 70%

Section: Glucose and Lacatementioning

confidence: 99%

Section: Glucose and Lacatementioning

confidence: 99%

Section: Glucose Utilization By Astrogliamentioning

confidence: 99%

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Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Takahashi

2020

Neuropathology

160

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“…Glutamate, an excitatory neurotransmitter essential for most brain activities, has been considered relevant to the pathogenesis of neuroinflammation, contributing to the development of several acute and chronic brain injuries [13]. The main process responsible for maintaining extracellular glutamate levels below toxic concentrations, thus favoring the physiological glutamatergic tonus, is the glutamate uptake activity of glutamate transporters located in neural cell membranes, mainly in astrocytes [14]. In this context, our group presented strong evidence that systemic guanosine (GUO) administration is effectively neuroprotective against glutamate toxicity and neuroinflammation in different protocols that mimic several brain disorders, in both in vitro and in vivo studies, Figure 2 [15].…”

Section: Lecture Highlightsmentioning

confidence: 99%

Neuroinflammation and Neuromodulation in Neurological Diseases

Robinson-Agramonte

Gonçalves

Almeida

et al. 2019

Behavioral Sciences

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Neuroimmunology is a relatively young science. This discipline has emerged today from the research field as a mature and fully developed innovative research area that integrates not only pure topics of neuroimmunology, but also expands on wider fields such as neuroplasticity, neuronal reserve and neuromodulation in association with clinical events, amongst which behavioral disorders stand out. The Cuban School of Neuroimmunology—a recent meeting that took place in Havana, Cuba—focused on topics based on the molecular mechanisms of neuroinflammation in neurological disorders involving behavioral manifestations, such as multiple sclerosis (MS), autism, cerebellar ataxias, Alzheimer´s disease and stroke among others, as well as on the use of new interventional technologies in neurology. Professor Luis Velazquez, from the Cuban Academy of Sciences, dictated an interesting lecture on Spinocerebellar ataxias, a genetic disorder where recent hypotheses related to the influence of neuroinflammation as a neurobiological factor influencing the progression of this disease have emerged. At the same time, the use of new interventional technologies in neurology was discussed, including those referring to novel disease modifying therapies in the course of MS and the use of transcranial magnetic stimulation in several neurological diseases, the latter reinforcing how interventional strategies in the form of non-invasive bran stimulation can contribute to physical rehabilitation in neurology. This paper summarizes the highlights of the most relevant topics presented during the First Cuban School of Neuroimmunology, organized by the Cuban Network of Neuroimmunology, held in June 2019.

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Molecular Signature of Astrocytes for Gene Delivery by the Synthetic Adeno‐Associated Viral Vector rAAV9P1

Bauer

Puglisi²,

Nagl

et al. 2022

Advanced Science

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Astrocytes have crucial functions in the central nervous system (CNS) and are major players in many CNS diseases. Research on astrocyte-centered diseases requires efficient and well-characterized gene transfer vectors. Vectors derived from the Adeno-associated virus serotype 9 (AAV9) target astrocytes in the brains of rodents and nonhuman primates. A recombinant (r) synthetic peptide-displaying AAV9 variant, rAAV9P1, that efficiently and selectively transduces cultured human astrocytes, has been described previously. Here, it is shown that rAAV9P1 retains astrocyte-targeting properties upon intravenous injection in mice. Detailed analysis of putative receptors on human astrocytes shows that rAAV9P1 utilizes integrin subunits 𝜶v, 𝜷8, and either 𝜷3 or 𝜷5 as well as the AAV receptor AAVR. This receptor pattern is distinct from that of vectors derived from wildtype AAV2 or AAV9. Furthermore, a CRISPR/Cas9 genome-wide knockout screening revealed the involvement of several astrocyte-associated intracellular signaling pathways in the transduction of human astrocytes by rAAV9P1. This study delineates the unique receptor and intracellular pathway signatures utilized by rAAV9P1 for targeting human astrocytes. These results enhance the understanding of the transduction biology of synthetic rAAV vectors for astrocytes and can promote the development of advanced astrocyte-selective gene delivery vehicles for research and clinical applications.

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The astrocyte biochemistry

Cited by 48 publications

References 131 publications

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Metabolic compartmentalization between astroglia and neurons in physiological and pathophysiological conditions of the neurovascular unit

Neuroinflammation and Neuromodulation in Neurological Diseases

Molecular Signature of Astrocytes for Gene Delivery by the Synthetic Adeno‐Associated Viral Vector rAAV9P1

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