Oleic Acid and Cholinergic dysfunction in Down Syndrome Models of the Central Nervous System

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Down syndrome (DS): or trisomy 21: is the most common autosomal aneuploidy and the leading genetic cause of intellectual disability. It is widely established that mental retardation is primarily a consequence of brain functioning and developmental abnormalities in neurogenesis. Some changes in the physical structure of the dendrites are a major cause of impaired synaptic plasticity of DS. The overexpression of the dual specificyty tyrsone phosphorylation-regulated kinase 1A (DYRK1A): located on chromosome 21: is involved in cellular plasticity and responsible for central nervous system disturbance in DS. Oleic acid is a neurotrophic factor that promotes neuronal differentiation and increases the levels of choline acetyltransferase (ChAT). Furthermore: it has recently been shown that it induces migration and formation of new synapses in euploid cells. However: remarkably oleic acid fails to reproduce the same effects in trisomic cells. Here we review the hypothesis that oleic acid-dependent synaptic plasticity may be dependent on the lipid environment. Thus: differences in membrane composition may be essential to understand why oleic acid promotes higher cell plasticity in euploid than in trisomic cells.