Journal
CELL REPORTS
Volume 41, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.111474
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Funding
- NIH [5R21DA038458, 1R01NS102272, T32GM008151, 1K99AG061231, 1T32GM139774-01]
- NSF [DGE-1745038]
- ZonMw [7330508160]
- WUSTL BioSURF program
- NIH through the CTSA [UL1 TR000448]
- Siteman Cancer Center [P30 CA91842]
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Neuronal activity can regulate transcriptional and translational responses in astrocytes, providing an additional mechanism for astrocytes to dynamically modulate nervous system functioning.
Within eukaryotic cells, translation is regulated independent of transcription, enabling nuanced, localized, and rapid responses to stimuli. Neurons respond transcriptionally and translationally to synaptic activity. Although transcriptional responses are documented in astrocytes, here we test whether astrocytes have pro-grammed translational responses. We show that seizure activity rapidly changes the transcripts on astrocyte ribosomes, some predicted to be downstream of BDNF signaling. In acute slices, we quantify the extent to which cues of neuronal activity activate translation in astrocytes and show that this translational response requires the presence of neurons, indicating that the response is non-cell autonomous. We also show that this induction of new translation extends into the periphery of astrocytes. Finally, synaptic proteomics show that new translation is required for changes that occur in perisynaptic astrocyte protein composition after fear conditioning. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.
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