ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurogenomics
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1603486
Cell types and neuronal genetic architecture in the rat CSF-contacting nucleus and the role of 5-HT in this nucleus in mediating morphine addiction through the brain-CSF circuit
Provisionally accepted
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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This study systematically characterized the cellular composition and functional characteristics of the CSF-contacting nucleus using single-cell RNA sequencing technology, while investigating its mechanistic role in morphine addiction. Single-cell RNA sequencing revealed that the CSF-contacting nucleus had an average of 22,046 genes expressed per cell. Unsupervised clustering revealed 25 cellular subsets belonging to five canonical CNS cell types (neuron, astrocyte, oligodendrocyte, microglia, endothelial) as annotated against the Genomics RNAseq database. The raw sequencing data have been deposited in the China National Center for Bioinformation (CNCB) accession number: CRR790158.GO and KEGG enrichment analyses demonstrated that the CSF-contacting nucleus neurons were significantly enriched in calcium signaling pathways, neurotransmitter regulation, and addiction-related pathways (including morphine, cocaine, and other substances).Given prior reports of morphine-induced alterations in CSF composition and the unique anatomical features of the CSF-contacting nucleus, we performed additional experimental validation. Chemogenetic manipulation experiments demonstrated that inhibition of the CSF-contacting nucleus attenuated morphine-induced CPP, UPLC-MS and ELISA revealed a marked increase in 5-HT levels in the CSF of the morphine addiction group. Knock out and chemogenetic inhibition of the CSF-contacting nucleus led to a significant reduction in CSF 5-HT levels. These findings suggest that the CSF-contacting nucleus may facilitate morphine addiction through regulated 5-HT release into the CSF. This discovery provides new experimental evidence for understanding CSF-mediated neuromodulation mechanisms.
Keywords: The CSF-contacting nucleus, 10X single-cell sequencing, Kyoto Encyclopedia of Genes and Genomes, 5-hydroxytryptamine (5-HT), morphine addiction
Received: 31 Mar 2025; Accepted: 16 May 2025.
Copyright: © 2025 Li, Gui, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Licai Zhang, Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
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