microRNAs expression correlates with levels of APP, DYRK1A, hyperphosphorylated Tau and BDNF in the hippocampus of a mouse model for Down syndrome during ageing.
Since the positive effect of exercise was paralleled by increased BDNF expression in trisomic mice, we investigated the effectiveness of a BDNF-mimetic treatment with 7,8-dihydroxyflavone at alleviating intellectual disabilities in the DS model.
These results uncover a critical link between calcineurin signalling, impaired neurotrophin trafficking and neurodevelopmental deficits in the peripheral nervous system in Down syndrome.
Repetitive oral administration of Neurotropin (200NU/kg/day, 3months) prevented the age-dependent decline in hippocampal BDNF expression in Ts65Dn mice, a model of Down's syndrome.
Two of the three A beta transgenic strains (APP(NLh) and TgCRND8) exhibited significantly decreased cortical BDNF mRNA levels compared with wild-type mice, whereas neither the other strain (APP(swe)/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected.
Two papers in this issue of Neuron show that reduced retrograde transport or signaling of the neurotrophins NGF or BDNF, respectively, may account for the neuronal pathology in mouse models of Down's syndrome.