Early-life stress of limited bedding/nesting material induced recognition memory loss and decreased hippocampal VGluT1 and nectin3 levels in aged male mice

Exposure to early-life stress has been found to lead to enduring psychiatric symptoms, including cognitive impairments that persist into adulthood and even old age. In this study, we investigated the behavioral effects and molecular changes of a well-established animal model of early-life stress, the limited bedding and nesting (LBN) model, in aged male mice. After 16 months, stressed mice showed a marked impairment in novel and spatial object recognition tasks, but not in temporal order memory or spatial working memory in the Y-maze spontaneous alternation task. These cognitive deficits were accompanied by a reduction in VGluT1 expression and a lower VGluT1/VGAT ratio in the CA1 region of the hippocampus, as well as reduced nectin3 expression in the mouse hippocampus. No significant molecular alterations were observed in the medial prefrontal cortex. These data support the notion that early-life stress leads to cognitive impairments in aged male mice, and these effects may be associated with a dysregulated excitatory/inhibitory balance and reduced nectin3 levels in the hippocampus.