Gene expression induced by DREADD activation in cultured astrocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE316854 | GEO | 2026/01/22
REPOSITORIES: GEO
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Project description:Astrocytes are the most common glial cell type in the brain, yet, it is still not clear how their activation affects the transcriptome of neighboring microglia and neurons. Engineered G protein-coupled receptors (GPCRs) called Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) make it possible to selectively activate specific cell types, such as neurons and astrocytes. By combining the selective activation of astrocytes with single cell RNA sequencing, we were able to study transcriptional changes that occur in response to the activation of astrocytes at the single cell level. Interestingly, our data shows that long-term activation of astrocytes in healthy mice results in dramatic alteration in the transcriptome of astrocytes and microglia. Genes that were differentially expressed in these Gq-DREADD-activated astrocytes were involved in neurogenesis and low-density lipoprotein particle biology, while those in the microglia were involved in lipoprotein handling, purinergic receptor activity, and immune cell migration and chemotaxis. Furthermore, network analysis showed that Gq-DREADD-mediated activation in astrocytes resulted in an upregulation of genes involved in the GPCR signaling pathways and calcium ion homeostasis, confirming astrocyte activation through Gq-DREADD expression. Our findings show the importance of considering transcriptomic alterations in microglia after the activation of astrocytes in in vivo models. Therefore, our data will serve as a resource for the broader neuroscience community.
2023-07-09 | GSE154208 | GEO
Project description:Neurons induce a dramatic transformation in developing astrocytes, causing them to develop a complex stellate morphology resembling their appearance in vivo. However, the transcriptional changes that accompany this transformation are not known, nor are the signalling mechanisms responsible. Similarly, whether synaptic activity controls astrocytic gene expression and whether this leads to altered astrocytic function is unclear. This experiment seeks to investigate this non-cell-autonomously regulated gene expression by co-culturing astrocytes and neurons derived from closely related species (mouse and rat), and separating RNA-seq reads derived from each cell type in silico, thus shedding light on the signalling mechanisms underlying neuron-to-astrocyte communication and the functional consequences for astrocytes.
2017-05-02 | E-MTAB-5514 | biostudies-arrayexpress
Project description:Aubert2005 - Interaction between astrocytes
and neurons on energy metabolism
Enocded non-curated model. Issues:
- Confusing equations A.41 and A.42
- Missing values for parameters Vv,0 and dHb,0
This model is described in the article:
Interaction between
astrocytes and neurons studied using a mathematical model of
compartmentalized energy metabolism.
Aubert A, Costalat R.
J. Cereb. Blood Flow Metab. 2005 Nov;
25(11): 1476-1490
Abstract:
Understanding cerebral energy metabolism in neurons and
astrocytes is necessary for the interpretation of functional
brain imaging data. It has been suggested that astrocytes can
provide lactate as an energy fuel to neurons, a process
referred to as astrocyte-neuron lactate shuttle (ANLS). Some
authors challenged this hypothesis, defending the classical
view that glucose is the major energy substrate of neurons, at
rest as well as in response to a stimulation. To test the ANLS
hypothesis from a theoretical point of view, we developed a
mathematical model of compartmentalized energy metabolism
between neurons and astrocytes, adopting hypotheses highly
unfavorable to ANLS. Simulation results can be divided between
two groups, depending on the relative neuron versus astrocyte
stimulation. If this ratio is low, ANLS is observed during all
the stimulus and poststimulus periods (continuous ANLS), but a
high ratio induces ANLS only at the beginning of the stimulus
and during the poststimulus period (triphasic behavior).
Finally, our results show that current experimental data on
lactate kinetics are compatible with the ANLS hypothesis, and
that it is essential to assess the neuronal and astrocytic
NADH/NAD+ ratio changes to test the ANLS hypothesis.
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MODEL1411210000.
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2015-02-25 | MODEL1411210000 | BioModels
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