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Although data indicate that perinatal maternal choline supplementation (MCS) alters the structure and function of these neurons in the Ts65Dn mouse model of DS and AD (Ts), whether MCS affects the molecular profile of vulnerable BFCNs remains\u00a0unknown. We investigated the genetic signature of BFCNs obtained from Ts and disomic (2N) offspring of Ts65Dn dams maintained on a MCS diet (Ts+, 2N+) or a choline normal diet (ND) from mating until weaning, then maintained on ND until 4.4\u20137.5\u00a0months of age. Brains were then collected and prepared for choline acetyltransferase (ChAT) immunohistochemistry and laser capture microdissection followed by RNA extraction and custom\u2010designed microarray analysis. Findings revealed upregulation of select transcripts in classes of genes related to the cytoskeleton (<jats:italic>Tubb4b<\/jats:italic>), AD (<jats:italic>Cav1<\/jats:italic>), cell death (<jats:italic>Bcl2<\/jats:italic>), presynaptic (<jats:italic>Syngr1<\/jats:italic>), immediate early (<jats:italic>Fosb, Arc<\/jats:italic>), G protein signaling (<jats:italic>Gabarap, Rgs10<\/jats:italic>), and cholinergic neurotransmission (<jats:italic>Chrnb3<\/jats:italic>) in Ts compared to 2N mice, which were normalized with MCS. Moreover, significant downregulation was seen in select transcripts associated with the cytoskeleton (<jats:italic>Dync1h1<\/jats:italic>), intracellular signaling (<jats:italic>Itpka, Gng3<\/jats:italic>, and<jats:italic>Mlst8<\/jats:italic>), and cell death (<jats:italic>Ccng1<\/jats:italic>) in Ts compared to 2N mice that was normalized with MCS. This study provides insight into genotype\u2010dependent differences and the effects of MCS at the molecular level within a key vulnerable cell type in DS and AD.<\/jats:p>","DOI":"10.1002\/dneu.22700","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T09:11:55Z","timestamp":1558602715000},"page":"664-683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Maternal Choline Supplementation Alters Basal Forebrain Cholinergic Neuron Gene Expression in the Ts65Dn Mouse Model of Down Syndrome"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-8641","authenticated-orcid":false,"given":"Christy M.","family":"Kelley","sequence":"first","affiliation":[{"name":"Department of Neurobiology Barrow Neurological Institute Phoenix Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen 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