Genotype, age and gender interaction in regulating BDNF expression in TgCRND8 Alzheimer's disease mice

Alzheimer'd Disease (AD) and other aging-associated neurodegenerative disorders may be induced by dysregulation of neurotrophins. Among these, Brain Derived Neurotrophic Factor (BDNF) is responsible for maturation and function of neurons in both peripheral and central nervous systems in the developing brain and has been shown to play a critical role in neuronal survival and in functional and structural synaptic plasticity. A direct role for BDNF/TrkB signalling in Aβ production, tau hyperphosphorylation and cognition decline in AD has been postulated. Aim of this work was to compare BDNF expression profiles in neurodevelopment and aging in an AD model. To this end, TgCRND8 mice (carrying the Indiana/Swedish double-mutated human APP transgene) and 129sv WT littermates were sacrificed at E14.5 and at PN30 and PN90 (i.e. before and after amyloid plaques deposition). BDNF expression in several brain areas was assessed by Real-Time PCR and by immunohistochemistry with particular attention to regional and sub-regional differences. BDNF promoter methylation was assessed by bisulfite modification of genomic DNA