Long-term social isolation exacerbates the impairment of spatial working memory in APP/PS1 transgenic mice

The interaction between gene and environment is known to play a major role in the etiology of several neuropsychiatric disorders, including Alzheimer's disease (AD). The present study evaluated whether environmental manipulations such as social isolation may affect the genetic predisposition to accelerate the onset of AD-related symptoms in an adult APP/PS1 double mutant transgenic mouse model. Transgenic and wild-type male mice were housed either singly or in groups from the age of 3 months, and their behavior was compared at 7 months. Isolation had several effects on the APP/PS1 transgenic mice, including exacerbating the impairment of spatial working memory associated with increased Aβ42/Aβ40 ratio in the hippocampus; increased levels of MnSOD in the CA1-CA3 subregions of the hippocampus, basolateral part of the amygdala (BLA), and locus coeruleus (LC); and decreased numbers of cholinergic cells in the diagonal band of Broca (DB), noradrenergic neurons in LC, serotonergic neurons in the Raphe nucleus, and levels of NMDA 2B receptor (NR2B) in the hippocampus region. Our findings demonstrate the susceptibility of APP/PS1 transgenic adult male mice to environmental manipulation and show that social isolation has remarkable effects on the genetically determined AD-like symptoms.