Mid-life stress and cognitive deficits during early aging in rats: individual differences and hippocampal correlates

We explored here the possibility that mid-life stress in rats could have deleterious effects on cognitive abilities during early aging, as well as the potential role of inter-individual differences on the development of such effects. Male Wistar rats were classified according to their reactivity to novelty (4 months old) as highly (HR) or low (LR) reactive and, at mid-life (12 months old), either submitted to chronic stress (28 days) or left undisturbed. At early aging (18 months old), their learning abilities were tested in the water maze, and a number of neuroendocrine (plasma corticosterone; hippocampal corticosteroid receptors) and neurobiological (hippocampal expression of neuronal cell adhesion molecules) parameters were evaluated. Impaired performance was observed in stressed HR rats, as compared to unstressed HR and stressed LR rats. Increased hippocampal mineralocorticoid receptors were found in stressed LR rats when compared with stressed HR and control LR groups. In addition, mid-life stress-induced an increased corticosterone response and a reduction in NCAM-180 isoform and L1 regardless of the behavioral trait of novelty reactivity. These findings highlight a role of stress experienced throughout life on cognitive impairment occurring during the early aging period, as well as the importance of taking into account individual differences to understand variability in such cognitive decline.