{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:01:15Z","timestamp":1781028075813,"version":"3.54.1"},"reference-count":81,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007353","name":"Jerome Lejeune Foundation USA","doi-asserted-by":"publisher","award":["1999"],"award-info":[{"award-number":["1999"]}],"id":[{"id":"10.13039\/100007353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007353","name":"Jerome Lejeune Foundation USA","doi-asserted-by":"publisher","award":["NIH NIAMS AR078663 to RJR"],"award-info":[{"award-number":["NIH NIAMS AR078663 to RJR"]}],"id":[{"id":"10.13039\/100007353","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["1999"],"award-info":[{"award-number":["1999"]}]},{"name":"NIH","award":["NIH NIAMS AR078663 to RJR"],"award-info":[{"award-number":["NIH NIAMS AR078663 to RJR"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS.<\/jats:p>","DOI":"10.3390\/genes15040452","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T03:37:21Z","timestamp":1712115441000},"page":"452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6859-2626","authenticated-orcid":false,"given":"S. Hossein","family":"Fatemi","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elysabeth D.","family":"Otte","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Folsom","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0508","authenticated-orcid":false,"given":"Arthur C.","family":"Eschenlauer","sequence":"additional","affiliation":[{"name":"Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Roper","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University-Purdue University, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin W.","family":"Aman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Thuras","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School and VA Health Care System, One Veterans Drive, Minneapolis, MN 55417, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","first-page":"962","article-title":"Chromosomal diagnosis of mongolism","volume":"16","author":"Lejeune","year":"1959","journal-title":"Arch. 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