Environmental enrichment rescues visual memory deficits in a mouse model of Alzheimer disease

Alzheimer’s Disease (AD) is by far the most frequent cause of dementia, affecting more than 12 million patients worldwide. Effective therapeutical strategies in AD are lacking. EE has recently emerged as a potential non invasive therapeutical strategy that might influence the onset and progression of human neurodegenerative diseases including AD. EE exerts indeed neuroprotective actions, slows the disease progression in a mouse model for Huntington disease, potentiates cortical plasticity, increases in the brain the expression of NT and of other factors of potential impact on AD. In mouse models of familial AD exposed to early onset EE Lazarov et al. (2005) have shown that exposure to EE of young transgenic mice reduces Aβ levels and Jankowsky et al. (2005) that EE has positive effects on spatial memory, although this was accompanied by an increase in Aβ levels. We have recently demonstrated that EE starting at two months of age, that is before the onset of cognitive deficits, completely prevents the onset of visual and spatial memory deficits in AD11 mice, a comprehensive mouse model for AD, reducing Aβ burden and rescuing the cholinergic deficit. AD11 mice, which express anti nerve growth factor (NGF) antibodies, develop an age dependent ND which encompasses all hallmarks of human AD. It is unknown whether EE is effective in rescuing memory deficits, once established, in aged AD11 mice. We have tested the efficacy of EE starting from 8 months of age, that is after the onset of behavioural deficits and the appearance of AD neuropathological hallmarks in AD11 mice. At 10 months of age, visual recognition memory was tested with the Object Recognition Test (ORT) with different retention intervals. We found that EE from 8 to 10 months of age completely rescues visual memory deficits in aged AD11 mice. These results show for the first time that it is possible to revert the progression of cognitive decline in a mouse model of AD by using non invasive therapeutical strategies which exert neuroprotective effects, thus supporting the efficacy of EE as a potential therapeutic strategy in AD.