BDNF intranasal administration rescues visual memory deficits in a mouse model of Alzheimer disease (AD), the AD11 mouse

We have recently demonstrated that environmental enrichment (EE) starting after the onset of behavioural deficits and the appearance of AD neuropathological hallmarks rescues visual memory (VM) deficits in aged AD11 mice (Berardi et al., 2006). AD11 mice, which express anti nerve growth factor (NGF) antibodies, develop an age dependent neurodegeneration which encompasses all hallmarks of human AD and appear to be a comprehensive mouse model for sporadic AD (Capsoni et al., 2000). The mechanisms underlying these beneficial effects of EE in AD11 mice are still unknown. It has been suggested that a crucial component of EE effects is the increase in neurotrophin (NT) expression found in the brain of EE animals. NT are considered potentially useful therapeutic agents in neurodegenerative diseases, given their control of cortical plasticity and their neuroprotective actions. A non invasive intranasal route to administer a NT, NGF, to the brain of AD11 mice has been recently employed, leading to a rescue of neuropathological markers (Capsoni et al 2002), as well as of VM deficits (De Rosa et al., 2005) in AD11 mice. We now tested whether BDNF intranasal administration, starting after the onset of cognitive and anatomical deficits, could rescue VM deficits in aged AD11 mice. We found that intranasal administration of BDNF for two weeks rescues VM deficits both at the 1 h and 24 hours retention interval. All BDNF treated animals showed a strong increase in their performance with respect to the ”before treatment” assessement. By converse, PBS treated, control AD11 mice showed no improvement, remaining at the very low performance levels typical of 7 months old AD11 mice. These results show that it is possible to revert the progression of cognitive decline in a mouse model of AD by non invasive intranasal administration of BDNF and suggest that BDNF increase found in EE animals is a crucial factor for the beneficial effects of EE in AD animal models. Telethon grant GGP030416.