Neurotrophic effects of Cerebrolysin in the Mecp2(308/Y) transgenic model of Rett syndrome.

Rett syndrome is a childhood neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG-binding protein (MeCP2). Neuropathological studies in patients with Rett syndrome and in MeCP2 mutant models have shown reduced dendritic arborization and abnormal neuronal packing. We have previously shown that Cerebrolysin (CBL), a neurotrophic peptide mixture, ameliorates the synaptic and dendritic pathology in models of aging and neurodegeneration. This study aimed to determine whether CBL was capable of reducing behavioral and neuronal alterations in Mecp2(308/Y) mutant mice. Two sets of experiments were performed, the first with 4-month-old male Mecp2(308/Y) mutant mice treated with CBL or vehicle for 3 months (Group A) and the second with 1-month-old mice treated for 6 months (Group B). Behavioral analysis showed improved motor performance with CBL in Group A and a trend toward improvement in Group B. Consistent with behavioral findings, neuropathological analysis of the basal ganglia showed amelioration of dendritic simplification in CBL-treated Mecp2(308/Y) mutant mice. CBL treatment also ameliorated dendritic pathology and neuronal loss in the hippocampus and neocortex in Mecp2(308/Y) mutant mice. In conclusion, this study demonstrates that CBL promotes recovery of dendritic and neuronal damage and behavioral improvements in young adult Mecp2(308/Y) mutant mice and suggests that CBL may have neurotrophic effects in this model. These findings support the possibility that CBL may have beneficial effects in the management of Rett syndrome.