Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila

Park, Annie; Croset, Vincent; Otto, Nils; Agarwal, Devika; Treiber, Christoph Daniel; Meschi, Eleonora; Sims, David; Waddell, Scott

doi:10.1016/j.cub.2022.07.038

Cited by 22 publications

(9 citation statements)

References 175 publications

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“…Due to the heterogeneity in the size and shape of glial cells, adult fly brain cells were suspended into single cells and sorted by the criteria whether the cells express GFP ( Figure 1B ). Interestingly, the sorting plot revealed that 8–10% of total cells were GFP-positive, correlating with the reported number of glia in adult fly brains ( Croset et al, 2018 ; Brunet Avalos et al, 2019 ; Park et al, 2022 ). After removal of cell debris, single GFP-positive glial cells were visualized by confocal microscopy ( Figure 1C ).…”

Section: Resultssupporting

confidence: 69%

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis

Wang,

2023

Front. Neural Circuits

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Fundamental properties of neurons and glia are distinctively different. Neurons are excitable cells that transmit information, whereas glia have long been considered as passive bystanders. Recently, the concept of tripartite synapse is proposed that glia are structurally and functionally incorporated into the synapse, the basic unit of information processing in the brains. It has then become intriguing how glia actively communicate with the presynaptic and postsynaptic compartments to influence the signal transmission. Here we present a thorough analysis at the transcriptional level on how glia respond to different types of neurotransmitters. Adult fly glia were purified from brains incubated with different types of neurotransmitters ex vivo. Subsequent RNA-sequencing analyses reveal distinct and overlapping patterns for these transcriptomes. Whereas Acetylcholine (ACh) and Glutamate (Glu) more vigorously activate glial gene expression, GABA retains its inhibitory effect. All neurotransmitters fail to trigger a significant change in the expression of their synthesis enzymes, yet Glu triggers increased expression of neurotransmitter receptors including its own and nAChRs. Expressions of transporters for GABA and Glutamate are under diverse controls from DA, GABA, and Glu, suggesting that the evoked intracellular pathways by these neurotransmitters are interconnected. Furthermore, changes in the expression of genes involved in calcium signaling also functionally predict the change in the glial activity. Finally, neurotransmitters also trigger a general metabolic suppression in glia except the DA, which upregulates a number of genes involved in transporting nutrients and amino acids. Our findings fundamentally dissect the transcriptional change in glia facing neuronal challenges; these results provide insights on how glia and neurons crosstalk in a synaptic context and underlie the mechanism of brain function and behavior.

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Section: Resultssupporting

confidence: 69%

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis

Wang,

2023

Front. Neural Circuits

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“…There is also evidence that microglia affect astrocyte activity through ATP release ( 67 ). These findings from both in vitro and in vivo models suggest that astrocytes play a proactive role in the transmission of information between neurons ( 91 , 92 ). D-type serine released from astrocytes had an active effect on NMDARs in cellular and animal experiments, especially on the GluN2A and GluN2B subunits ( 93 ).…”

Section: Role Of Astrocytes In Lidmentioning

confidence: 86%

Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation

Zhang,

Liu,

Tuo

et al. 2023

Front. Immunol.

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Parkinson’s disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the “on-off phenomenon”, decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.

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“… 93 , 95 , 116 , 117 At the neuromuscular junction, glutamate primarily excites. 94 We calculated from single-cell RNA sequencing 118 that ∼80% of neurons in the central brain express RNA transcripts for GluClAlpha as well as at least one excitatory ionotropic glutamate receptor. The sign of a glutamatergic connection may depend on the sub-localization and ratio of receptors at recipient sites.…”

Section: Discussionmentioning

confidence: 99%

Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster

Eckstein,

Bates,

Champion

et al. 2024

Cell

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Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila

Cited by 22 publications

References 175 publications

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis

Profiling neurotransmitter-evoked glial responses by RNA-sequencing analysis

Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation

Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster

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