Astrocyte Activation Markers

Gorina, Yana V.; Салмина, А. Б.; Ерофеев, А. И.; Gerasimov, Evgeniy I.; Bolshakova, Anastasia; Balaban, Pavel M.; Bezprozvanny, Ilya; Власова, О. Л.

doi:10.1134/s0006297922090012

Cited by 4 publications

(3 citation statements)

References 172 publications

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“…This observation may indicate premature senescence and differentiation, in agreement with the reduced cell viability and proliferative capacity measured in patient-derived iPSCs [ 11 , 25 ]. To characterize iAs, we evaluated an extensive set of astrocytic markers, including GFAP , S100ß , ALDH1L1 , AQP4 , APOE , GLAST , and GLT-1 [ 26 , 27 , 28 ]. All markers exhibited significantly higher expression in iAs compared to NPCs, confirming their higher degree of astroglial differentiation.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient

Arribas-Carreira,

Castro,

García

et al. 2024

IJMS

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The pathophysiology of nonketotic hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neural model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance, and protein analyses. This study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine–glycine–one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Our analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology of nonketotic hyperglycinemia and offer new perspectives for therapeutic options.

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Section: Discussionmentioning

confidence: 99%

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient

Arribas-Carreira,

Castro,

García

et al. 2024

IJMS

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“…At the same time, assuming the release of D-serine by astrocytes, there is a possibility of hyperactivating NMDA receptors, which already have an increased level of activity due to αβ-amyloid toxicity and elevated levels of Ca2+ [ 81 , 82 ]. In combination with D-serine, a wide range of only excitatory, and, probably, inhibitory neurotransmitters and neuromodulators are released [ 83 , 84 , 85 , 86 ]. These together cause a positive effect on the restoration of the formation of long-term potentiation and improvement of the cognitive functions of transgenic mice of the 5xFAD line.…”

Section: Discussionmentioning

confidence: 99%

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

Gerasimov

Bezprozvanny

Власова

2023

IJMS

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Alzheimer’s disease (AD) is one of the most widespread neurodegenerative diseases. Most of the current AD therapeutic developments are directed towards improving neuronal cell function or facilitating Aβ amyloid clearance from the brain. However, some recent evidence suggests that astrocytes may play a significant role in the pathogenesis of AD. In this paper, we evaluated the effects of the optogenetic activation of Gq-coupled exogenous receptors expressed in astrocytes as a possible way of restoring brain function in the AD mouse model. We evaluated the effects of the optogenetic activation of astrocytes on long-term potentiation, spinal morphology and behavioral readouts in 5xFAD mouse model of AD. We determined that in vivo chronic activation of astrocytes resulted in the preservation of spine density, increased mushroom spine survival, and improved performance in cognitive behavioral tests. Furthermore, chronic optogenetic stimulation of astrocytes resulted in the elevation of EAAT-2 glutamate uptake transporter expression, which could be a possible explanation for the observed in vivo neuroprotective effects. The obtained results suggest that the persistent activation of astrocytes may be considered a potential therapeutic approach for the treatment of AD and possibly other neurodegenerative disorders.

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“…The goal is to provide sufficient knowledge of the state-of-the-art techniques for visualizing and manipulating astrocytes to help researchers choose the right approach for their biological questions. Greater detail is beyond our scope and can be found elsewhere [6,[58][59][60][61].…”

Section: Available Methods For Tracking Astrocytesmentioning

confidence: 99%

Shining the Light on Astrocytic Ensembles

Delgado

Navarrete

2023

Cells

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While neurons have traditionally been considered the primary players in information processing, the role of astrocytes in this mechanism has largely been overlooked due to experimental constraints. In this review, we propose that astrocytic ensembles are active working groups that contribute significantly to animal conduct and suggest that studying the maps of these ensembles in conjunction with neurons is crucial for a more comprehensive understanding of behavior. We also discuss available methods for studying astrocytes and argue that these ensembles, complementarily with neurons, code and integrate complex behaviors, potentially specializing in concrete functions.

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Astrocyte Activation Markers

Cited by 4 publications

References 172 publications

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient

Metabolic Rewiring and Altered Glial Differentiation in an iPSC-Derived Astrocyte Model Derived from a Nonketotic Hyperglycinemia Patient

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

Shining the Light on Astrocytic Ensembles

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