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- W4224277323 abstract "Neurons must function for decades of life, but how these non-dividing cells are preserved is poorly understood. Using mouse serotonin (5-HT) neurons as a model, we report an adult-stage transcriptional program specialized to ensure the preservation of neuronal connectivity. We uncover a switch in Lmx1b and Pet1 transcription factor function from controlling embryonic axonal growth to sustaining a transcriptomic signature of 5-HT connectivity comprising functionally diverse synaptic and axonal genes. Adult-stage deficiency of Lmx1b and Pet1 causes slowly progressing degeneration of 5-HT synapses and axons, increased susceptibility of 5-HT axons to neurotoxic injury, and abnormal stress responses. Axon degeneration occurs in a die back pattern and is accompanied by accumulation of α-synuclein and amyloid precursor protein in spheroids and mitochondrial fragmentation without cell body loss. Our findings suggest that neuronal connectivity is transcriptionally protected by maintenance of connectivity transcriptomes; progressive decay of such transcriptomes may contribute to age-related diseases of brain circuitry." @default.
- W4224277323 created "2022-04-26" @default.
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- W4224277323 date "2022-04-01" @default.
- W4224277323 modified "2023-10-17" @default.
- W4224277323 title "An adult-stage transcriptional program for survival of serotonergic connectivity" @default.
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- W4224277323 doi "https://doi.org/10.1016/j.celrep.2022.110711" @default.
- W4224277323 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35443166" @default.
- W4224277323 hasPublicationYear "2022" @default.
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