Neurodevelopmental disorders: Super sonic

摘要

Down syndrome, a major cause of intellectual disability, is caused by the inheritance of an extra copy of chromosome 21. Understanding how this genetic abnormality leads to alterations in brain development and cognitive function is essential for the development of effective therapeutic interventions. A new paper by Das et al. shows that an early enhancement of sonic hedgehog (SHH)-mediated signalling can counteract some of the deficits observed in a mouse model of Down syndrome.Mice that possess extra copies of subsets of the genes on chromosome 21 replicate some key features of Down syndrome, including a reduction in the number of granule cells (GCs) in the cerebellum and the hippocampal dentate gyrus. In the Ts65Dn mouse model, the cerebellar phenotype results from a reduced response to SHH — SHH signalling normally promotes GC precursor proliferation immediately after birth. The authors therefore boosted SHH signalling by administering a single dose of a SHH pathway agonist, SAG 1.1, at birth and examined its effects on the adult brain.At 16 weeks after birth, brain sections taken from untreated Ts65Dn mice confirmed that there was a reduction in cerebellar area and the density of cerebellar GCs in these mice. By contrast, GC density was corrected to wild-type levels in SAG 1.1-treated Ts65Dn mice, suggesting that the transient increase in GC proliferation at birth had long-lasting effects on cerebellar structure.