RNA-seq of iPSC-derived astrocytes that are capable of exerting pro-maturational effect on synaptic networks
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA629331 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11646510_1.fastq.gz | Fastqsanger.gz | |||
| SRR11646510_2.fastq.gz | Fastqsanger.gz | |||
| SRR11646511_1.fastq.gz | Fastqsanger.gz | |||
| SRR11646511_2.fastq.gz | Fastqsanger.gz | |||
| SRR11646512_1.fastq.gz | Fastqsanger.gz |
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Project description:Astrocytes are glial cells essential for neuronal plasticity. However, the role of astrocytic cAMP signalling in brain activity and function is still missing. We expressed DdPAC, a photoactivated adenylyl cyclase that increases cAMP upon red light, in cortical astrocytes to investigate its effects. We assessed synaptic transmission using multi-electrode arrays, and molecular changes through proteomic, phosphoproteomic, and metabolic analyses. We also measured brain hemodynamics and analysed motor behaviour in wild-type (WT) and R6/1 Huntington's disease (HD) mice. DdPAC stimulation in cortical astrocytes induced long-term synaptic potentiation in WT mice, which was PKA and NMDAR-dependent but Ca2+-independent. It also triggered PKA-signalling pathways and modulated synaptic and morphology-associated proteins. Further, cAMP signalling increased cortical blood flow and improved motor learning in WT mice but show differential responses in HD mice. Our results unravel the impact of cAMP signalling in astrocytes to synaptic to brain function, and highlight its alterations in HD.
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