{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324025/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324025"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Microglial sTREM2 limits dyskinesia and acts on TrkB to support circuit plasticity.","description":"Microglia continuously survey the brain and shape neuronal activity, but their contribution to experience-dependent synaptic plasticity is unclear. Levodopa-induced dyskinesia (LID) is a disabling complication of late-stage Parkinson’s disease (PD) that is linked to maladaptive striatal remodeling and is often assumed to reflect detrimental neuroinflammation. Here we identify a dyskinesia-associated microglial gene program in the striatum of PD patients and show that microglia instead act as a protective brake on LID. In a mouse model, microglial depletion exacerbated dyskinesia, whereas microglial repopulation mitigated it. Delivery of AAV expressing soluble TREM2 (sTREM2) similarly reduced LID without impairing the therapeutic benefit of levodopa. Single-nucleus transcriptomics revealed that microglial loss drives extensive remodeling of both direct and indirect spiny projection neurons (SPNs), while repopulation or sTREM2 reverses a large fraction of LID-associated transcriptional changes. Mechanistically, sTREM2 directly engages TrkB and potentiates BDNF-dependent TrkB–ERK signaling, consistent with positive allosteric modulation. Functionally, sTREM2 enhances BDNF-TrkB-dependent hsciippocampal synaptic plasticity and acutely rebalances striatal dendritic excitability in a compartment- and cell type-specific manner. These findings reveal an unexpected neuroimmune pathway in which microglia restrain maladaptive plasticity via sTREM2–TrkB signaling, with therapeutic implications.","dates":{"publication":"2026/08/03"},"accession":"GSE324025","cross_references":{"GSM":["GSM9566903","GSM9566902","GSM9566869","GSM9566868","GSM9566901","GSM9566867","GSM9566900","GSM9566866","GSM9566865","GSM9566864","GSM9566863","GSM9566862","GSM9566909","GSM9566908","GSM9566907","GSM9566906","GSM9566905","GSM9566904","GSM9566914","GSM9566913","GSM9566879","GSM9566912","GSM9566911","GSM9566878","GSM9566910","GSM9566877","GSM9566876","GSM9566875","GSM9566874","GSM9566873","GSM9566872","GSM9566871","GSM9566870","GSM9566919","GSM9566918","GSM9566917","GSM9566916","GSM9566915","GSM9566889","GSM9566888","GSM9566887","GSM9566920","GSM9566886","GSM9566885","GSM9566884","GSM9566883","GSM9566882","GSM9566881","GSM9566880","GSM9566899","GSM9566898","GSM9566897","GSM9566896","GSM9566895","GSM9566894","GSM9566893","GSM9566892","GSM9566891","GSM9566890"],"GPL":["24247"],"GSE":["324025"],"taxon":["Mus musculus"],"PMID":["[42146496]"]}}