Differential expression of Hdac2 in male and female mice of differing social status.

Mice naturally form social hierarchies, and their experiences as subordinate or dominant mice inform future behavioural strategies. To better understand the neural bases of social dominance, we investigated hippocampal gene and protein expression of histone deacetylase 2 (HDAC2), an epigenetic regulator that decreases expression of synaptic plasticity genes and reduces excitatory synaptic function. Hdac2 in hippocampus was associated with social status. The gene for a closely related histone deacetylase (Hdac1), and HDAC2 protein expression, were not associated with social rank in hippocampus. These findings suggest that Hdac2 expression in hippocampus is distinctly linked with social status.

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.