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Behavioral changes in patients are mirrored in\n                    <jats:italic>Foxp1<\/jats:italic>\n                    <jats:sup>\u00b1<\/jats:sup>\n                    mice. It is shown that decreased Foxp1 in the\n                    <jats:italic>Foxp1<\/jats:italic>\n                    <jats:sup>\u00b1<\/jats:sup>\n                    striatum results in a significant decrease in phosphodiesterase 10a (Pde10a). Predominantly expressed in medium spiny neurons (MSNs), Pde10a modulates basal ganglia circuitry. Furthermore, the\n                    <jats:italic>Foxp1<\/jats:italic>\n                    <jats:sup>\u00b1<\/jats:sup>\n                    striatum exhibits microglial activation, reduced synaptic pruning, and dysregulation of 111 inflammatory genes. These include the downregulated\n                    <jats:italic>P2ry12<\/jats:italic>\n                    and\n                    <jats:italic>Fcrls<\/jats:italic>\n                    , markers of homeostatic microglia, and upregulated\n                    <jats:italic>Cd74<\/jats:italic>\n                    , a marker of reactive microglia, suggesting that neuroinflammation contributes to the observed deficits. Interestingly, treatment of\n                    <jats:italic>\n                      Foxp1\n                      <jats:sup>\u00b1<\/jats:sup>\n                    <\/jats:italic>\n                    mice with the PDE10A antagonist MP\u201010 (PF\u20102545920) immediately after birth not only corrects behavioral abnormalities, including decreased ultrasonic vocalization, hyperactivity, and anxiety but also normalizes changes in microglia morphology and synaptic pruning. Transcriptomic analysis with a neuroinflammation\u2010specific gene panel reveals nominal gene expression changes after MP\u201010 treatment, including\n                    <jats:italic>Bdnf<\/jats:italic>\n                    upregulation and enrichment of neurotrophin signaling. Since FOXP1 and its signaling pathway are highly conserved, administration of MP\u201010 or other Pde10a antagonists may also alleviate the neurological dysfunction seen in humans with FOXP1 syndrome.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500623","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:28:52Z","timestamp":1750922932000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Phosphodiesterase 10A by MP\u201010 Rescues Behavioral Deficits and Normalizes Microglial Morphology and Synaptic Pruning in A Mouse Model of FOXP1 Syndrome"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-2034","authenticated-orcid":false,"given":"Henning","family":"Fr\u00f6hlich","sequence":"first","affiliation":[{"name":"Institute of Human Genetics Heidelberg University  69120 Heidelberg 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