{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE342nnn/GSE342037/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Rattus norvegicus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE342037"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Targeting NCAM1/FGFR1 signaling to alleviate sleep disturbance-induced neuroinflammation in the hypothalamus","description":"Sleep disturbance is a prevalent public health concern linked to cognitive deficits and emotional dysregulation, yet the underlying mechanisms by which SD leads to hypothalamic dysfunction remain poorly understood. We demonstrated that two-week SD induced significant neuroinflammation in the hypothalamus, characterized by elevated expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as the chemokine Ccl2, alongside progressive neuronal loss, as evidenced by reduced nissl bodies and NeuN+ cells. Single-nucleus RNA sequencing revealed that inhibitory neurons were the most responsive hypothalamic cell cluster to SD, exhibiting enriched pro-inflammatory pathways (e.g., TNF and IL-17 signaling) and neurodegenerative transcriptional programs. Furthermore, SD triggered microglial activation and a phenotypic shift toward a disease-associated state, with enhanced antigen-presenting and pro-inflammatory capacity. Notably, intercellular communication analysis identified the neural cell adhesion molecule 1 (NCAM1)/fibroblast growth factor receptor 1 (FGFR1) signaling axis as a key mediator of crosstalk between microglia and other cell types. In vitro experiments in BV2 cells revealed that NCAM1, via FGFR1, suppressed lipopolysaccharide-induced M1 polarization and the subsequent release of pro-inflammatory cytokines. Collectively, our findings elucidate a critical protective role for the NCAM1/FGFR1 axis in mitigating SD-induced hypothalamic neuroinflammation and neuronal injury, highlighting a potential therapeutic target for sleep-related neurological disorders.","dates":{"publication":"2026/08/07"},"accession":"GSE342037","cross_references":{"GSM":["GSM9922154","GSM9922155"],"GPL":["25947"],"GSE":["342037"],"taxon":["Rattus norvegicus"]}}