Abstract: Objectives: The brains of individuals with Down syndrome (DS) present defects in neurogenesis and synaptogenesis during prenatal and early postnatal stages that are partially responsible for their cognitive disabilities. Because oleic and linolenic fatty acids enhance neurogenesis, synaptogenesis, and cognitive abilities in rodents and humans, in this study we evaluated the ability of these compounds to restore these altered phenotypes in the Ts65Dn (TS) mouse model of DS during early postnatal stages. Methods: TS and euploid mice were treated with oleic or linolenic acid from PD3 to PD15, and the short- and long- term effects of these acids on neurogenesis and synaptogenesis were evaluated. The effects of these treatments on the cognitive abilities of TS mice during early adulthood were also evaluated. Results: Administration of oleic or linolenic acid did not modify cell proliferation immediately after treatment discontinuation or several weeks later. However, oleic acid increased the total number of DAPI+ cells (+ 26%), the percentage of BrdU+ cells that acquired a neural phenotype (+ 9.1%), the number of pre- (+ 29%) and post-synaptic (+ 32%) terminals and the cognitive abilities of TS mice (+ 18.1%). In contrast, linolenic acid only produced a slight cognitive improvement in TS mice. (+12.1%). Discussion: These results suggest that early postnatal administration of oleic acid could palliate the cognitive deficits of DS individuals.

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