Transcriptomics

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Galectin-3 activates microglia in arthritic pain: a process defective in Alzheimer’s disease mice


ABSTRACT: Musculoskeletal chronic pain is prevalent in individuals with Alzheimer’s Disease (AD) however, remains largely untreated in these patients, raising the possibility that pain mechanisms are perturbed in AD. Here we utilised the TASTPM transgenic mouse model of AD with the K/BxN serum transfer (ST) model of inflammatory arthritis. We show that inflammatory allodynia in WT is associated with release of galectin-3 (Gal-3) by nociceptive fibres in dorsal horn and a distinct TLR4-dependent transcriptional profile and upregulation of P2Y12 in microglia. In contrast, TASTPM show attenuated inflammatory allodynia which is not affected by a Gal-3 inhibitor and correlates with emergence of a subset of P2Y12- TLR4- microglia in the dorsal horn. We suggest that in WT, extracellular Gal-3, which is a TLR4 ligand, facilitates inflammatory allodynia through TLR4-regulated release of pro-nociceptive mediators by microglia. However, Gal-3 is not pro-nociceptive in TASTPM due to absence of TLR4 in microglia.

ORGANISM(S): Mus musculus

PROVIDER: GSE213157 | GEO | 2023/04/01

REPOSITORIES: GEO

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