biostudies-literatureMen YNICHD NIH HHSFRAXA Research FoundationNIMH NIH HHSNIAAA NIH HHSNINDS NIH HHSRobert J. Kleberg, Jr. and Helen C. Kleberg FoundationNIH25092-25103https://www.ebi.ac.uk/biostudies/studies/S-EPMC7547241biostudies-literatureUnknown117(40)The loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common inherited intellectual disability. How the loss of FMRP alters protein expression and astroglial functions remains essentially unknown. Here we showed that selective loss of astroglial FMRP in vivo up-regulates a brain-enriched miRNA, miR-128-3p, in mouse and human FMRP-deficient astroglia, which suppresses developmental expression of astroglial metabotropic glutamate receptor 5 (mGluR5), a major receptor in mediating developmental astroglia to neuron communication. Selective in vivo inhibition of miR-128-3p in FMRP-deficient astroglia sufficiently rescues decreased mGluR5 function, while astroglial overexpression of miR-128-3p strongly and selectively diminishes developmental astrogliaProceedings of the National Academy of Sciences of the United States of AmericaAstroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling.PMC7547241N/AR01 MH106490R01 MH118827R01 MH116582R01 MH113780R01 NS105200MH116582NS105339MH113780U54 HD090256MH106490R01 AA025128R21 NS105339Ye LMen YYang YPaukert MPromes VRisgaard RDZhao XfalseAstroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling.The loss of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common inherited intellectual disability. How the loss of FMRP alters protein expression and astroglial functions remains essentially unknown. Here we showed that selective loss of astroglial FMRP in vivo up-regulates a brain-enriched miRNA, miR-128-3p, in mouse and human FMRP-deficient astroglia, which suppresses developmental expression of astroglial metabotropic glutamate receptor 5 (mGluR5), a major receptor in mediating developmental astroglia to neuron communication. Selective in vivo inhibition of miR-128-3p in FMRP-deficient astroglia sufficiently rescues decreased mGluR5 function, while astroglial overexpression of miR-128-3p strongly and selectively diminishes developmental astroglia2020-01-01T00:00:00Z2020 Oct2025-04-04T11:53:51.697Z2025-04-04T11:53:51.697ZS-EPMC75472413295864710.1073/pnas.2014080117