The anxiogenic effects of adolescent psychological stress in male and female mice.

Adolescence is a period of transition during which there is extensive development of the brain and the hypothalamic-pituitary-adrenal axis. However, the term adolescence is broad and covers a number of important developmental periods ranging from pre-pubescence to sexual maturity. Using a predator stress model, we investigated the effects of chronic psychological stress on anxiety-like, depression-like, and social behaviours in male and female mice during early adolescence, when mice are pre-pubertal, and late adolescence, when mice are sexually mature. All stressed mice showed hyperactivity and increased anxiety-like behaviours. The anxiogenic effects were generally more pronounced in mice exposed to late, rather than early adolescent stress, but were clearly evident when stress was experienced at either timepoint. Risk assessment behaviours were also affected by the stress treatments, but the direction of these changes were sometimes sex- and age-specific. Surprisingly, mice stressed during adolescence showed no depressive-like behaviours as adults. This study provides evidence that adolescent psychological stress has pronounced long-term anxiogenic effects but that the precise behavioural phenotype differs based on sex and the sub-stage of adolescence during which the individual is exposed.

Age-related changes in social behaviours in the 5xFAD mouse model of Alzheimer's disease.

In addition to memory impairments, patients with Alzheimer's disease (AD) exhibit a number of behavioural and psychological symptoms that can affect social interactions over the course of the disease. While altered social interactions have been demonstrated in a number of mouse models of AD, many models only recapitulate the initial stages of the disease, and these behavioural changes have yet to be examined over the course of disease progression. By performing a longitudinal study using the 5xFAD mouse model, we have demonstrated that transgenic females exhibit progressive alterations in social investigation compared to wild-type controls. Transgenic females exhibited an age-related reduction in interest for social odours, as well as reduced investigative behaviours towards novel conspecifics in a novel environment. However, transgenic mice exhibited no obvious olfactory deficits, nor any changes in scent-marking behaviour compared to wild-type controls, indicating that changes in investigative behaviour were due to motivation to engage with a social stimulus. This evidence suggests that transgenic 5xFAD females exhibit increased social anxiety in novel environments compared to wild-type controls. Overall, transgenic 5xFAD female mice mimic some features of social withdrawal observed in human AD patients suggesting this strain may be suitable for modelling aspects of the social dysfunction observed in human patients.