Correlation of ERα/ERβ expression with dendritic and behavioural changes in CUMS mice

• CUMS increases the ratio of ERα/ERβ mRNA and protein expression.
• CUMS exposure decreases dendritic arborization but increases spine density.
• The increase in spine density is restricted to initial distance of dendrite length.

In response to chronic stress, oestrogen receptor (ER)α acts as an anxiogenic agent as opposed to ERβ which predominantly acts as an anxiolytic agent. These properties of ER play an important role in mediating anxiety- and depression-like behaviour and physiological responses. However, the precise underlying mechanism remains unclear. In particular, not much is known about the expression of ERα and ERβ in the stress-sensitive brain regions such as the prefrontal cortex, hippocampus and amygdala. Using a rodent model of chronic unpredictable mild stress (CUMS), we report that two weeks of CUMS in young male mice (10 ± 2 weeks) induces noteworthy changes in the ratio of ERα/ERβ in the prefrontal cortex and hippocampus. While we observed a significant (P < 0.05) increase in ERα mRNA and protein expression levels, the expression of ERβ in the prefrontal cortex, hippocampus and amygdala was significantly reduced. This increase in ERα expression with concomitant decrease in ERβ expression was associated with increased anxiety- and depression-like behaviour as observed in elevated plus maze test, open field test, forced swim test and sucrose preference test. In addition to these behavioural changes, we report the decrease of dendritic complexity with concomitant increase in spine density in the medial prefrontal cortex, dorsohippocampal CA3 region and basolateral complex of amygdala (BLA). Taken together, these results suggest that the CUMS-induced increase in the ratio of ERα/ERβ causes dendritic remodeling, which in turn might be responsible for increase in anxiety- and depression-like behaviour in young male mice.