Neuroanatomical study of a murine model for down syndrome

Down’s syndrome (DS) is the phenotypic expression of the partial or total trisomy of the chromosome 21. DS patients display visual deficits, impaired odour identification, inappropriate sexual and aggressive behaviour. Moreover, they are affected by mental retardation, and, in the adulthood, may develop anatomo-pathological alterations similar to those observed in the Alzheimer’s disease. Recently, partial trisomic chromosome 16 mice (Ts65Dn) have been developed that contain most of the genes from human chromosome 21. Several behavioural studies have been already performed on this animal model, confirming a very close parallelism with the DS behavioural deficits; on the contrary, only a few studies have investigated the neuroanatomical architecture of the Ts65Dn mouse brain. Because of its involvement in complex behaviors, including sexual and aggressive behaviors, we investigated the nitric oxide (NO) system in specific brain regions of these mutant mice (TS) after isolation-induced aggression. Male TS mice displayed significantly higher aggression than wild type (WT) mice and the comparison of the NO system, both with immunohistochemical and histochemical methods, resulted in robust differences between TS and WT mice in the hypothalamic paraventricular nucleus, in the nucleus of the diagonal band and in the medial septum, but not in the striatum of TS mice. In conclusion, we document alterations in the neuronal NO system of the TS mouse model of DS, suggesting a correlation of the behavioral aggressiveness with deficient NO production.