Alterations of brain circuits in Down syndrome murine models

Trisomy 21, also referred to Down syndrome (DS), is the most common genetic cause of mental retardation, affecting 1 each 800-1000 newborn children all over the world. DS is a complex disease, determined by an extra copy of human chromosome 21 that causes an imbalanced gene dose effect. The syntenies that exist between mouse chromosomes 10, 16, and 17 and human chromosome 21 offer the opportunity for a genotype-phenotype correlation and several mouse models of DS have been developed to improve our knowledge about cognitive disabilities and brain alterations. We present here the different murine models available up to now and we discuss the neural alterations that have been described in these strains. The largest amount of studies involved the so called Ts65Dn mouse showing early alterations of nitrergic, noradrenergic and cholinergic systems at the level of the basal forebrain. Neurogenesis and spine formations are decreased in the hippocampus, as well as the whole size of the cerebellum and the number of granule cells.