Cholinergic and nitrinergic system in the tegmental Nuclei of TS65DN mice, a murine model for down syndrome

The partially trisomic mice Ts65Dn have been largely used as animal model for the study of Down syndrome. These mice have a triplication of segment of mouse chromosome 16 syntenic to the so-called obligate region of human chromosome 21 and show several behavioral alterations like deficits in learning and memory as well as altered sexual and aggressive behaviors that, in humans, are related to Down Syndrome. Previous studies demonstrated a precocious (3 month-old) reduction of the nitrinergic system in the basal forebrain (Gotti et al, 2004) followed by that of cholinergic system (age 4-6 months; Granholm et al., 2000). These alterations have been observed in the medial septum and the nucleus of the diagonal band, where the two systems are largely co-existent. We have here investigated the nitrinergic and cholinergic systems in both basal forebrain and pontine tegmental nuclei, in male Ts65Dn mice at the age of 3 months. Our results indicate that co-localization of the two markers is extensive only at the level of pontine nuclei, whereas in the forebrain, they largely co-exist in the same regions, but rarely co-localize in the same cells. By means of quantitative analysis we demonstrated a significant reduction of the nitrinergic system only in the forebrain with no effect of mutation on the cholinergic system. On the contrary, both cholinergic and nitrinergic systems are unaffected at the pontine level. This is an intriguing feature, due to the fact that tegmental nuclei send and receive connections from the basal forebrain. It appears therefore that, in Ts65Dn mice, the precocious alterations of the nitrinergic system are very selective and circumscribed.