Cognitive and emotional profiles of aged Alzheimer's disease (3×TgAD) mice: Effects of environmental enrichment and sexual dimorphism

•Aged 3×TgAD mice show deficits in spatial learning, short-term and working memory.•3×TgAD mice show signs of increased anxiety and normal sensorimotor functions.•Sexual dimorphism is reflected by increased behavioral inhibition in males.•Sexual dimorphism is reflected by increased cognitive deficits in females.•Environmental enrichment in adulthood induces beneficial effects on working memory. Alzheimer's disease is a neurodegenerative disorder associated with age which represents the most common cause of dementia. It is characterized by an accelerated memory loss compared to normal aging, and deterioration of other cognitive abilities that interfere with mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are β-amyloid (βA) plaques and neurofibrillary Tau tangles. Triple transgenic 3×TgAD mouse model develops βA and Tau pathologies in a progressive manner, with a specific temporal and anatomic profile mimicking the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. Environmental enrichment treatment in mice induces behavioral and emotional reactivity changes, including cognitive improvements in some AD-related transgenic mice. The present work intended to characterize the behavioral profile of 3×TgAD mice at advanced stages of neuropathological development (12 and 15 months of age) and to investigate whether environmental enrichment administered during adulthood was able to modify some of their behavioral and cognitive alterations. Results show that, at advanced stages of the disease 3×TgAD mice show deficits of spatial learning acquisition, as well as short-term and working memory deficits, while displaying increased levels of anxiety/fearfulness and normal sensorimotor functions. 3×TgAD mice also show sexual dimorphism, as reflected by increased cognitive deficits in females and increased levels of novelty-induced behavioral inhibition in males. Environmental enrichment exerts some slight positive effects, by mainly improving the initial acquisition of the spatial learning and working memory in 12-month-old 3×TgAD mice. Such effects vary depending on the gender.