Sex-specific effects of social isolation on ageing in Drosophila melanogaster.
Leech Thomas,Sait Steven M,Bretman Amanda
Journal of insect physiology
Social environments can have a major impact on ageing profiles in many animals. However, such patterns in variation in ageing and their underlying mechanisms are not well understood, particularly because both social contact and isolation can be stressful. Here, we use Drosophila melanogaster fruitflies to examine sex-specific effects of social contact. We kept flies in isolation versus same-sex pairing throughout life, and measured actuarial (lifespan) and functional senescence (declines in climbing ability). To investigate underlying mechanisms, we determined whether an immune stress (wounding) interacted with effects of social contact, and assessed behaviours that could contribute to differences in ageing rates. Pairing reduced lifespan for both sexes, but the effect was greater for males. In contrast, pairing reduced the rate of decline in climbing ability for females, whereas for males, pairing caused more rapid declines with age. Wounding reduced lifespan for both sexes, but doubled the negative effect of pairing on male lifespan. We found no evidence that these effects are driven by behavioural interactions. These findings suggest that males and females are differentially sensitive to social contact, that environmental stressors can impact actuarial and functional senescence differently, and that these effects can interact with environmental stressors, such as immune challenges.
10.1016/j.jinsphys.2017.08.008
Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice.
Brain, behavior, and immunity
Unpredictable chronic mild stress (UCMS) is one of the most commonly used, robust and translatable models for studying the neurobiological basis of major depression. Although the model currently has multiple advantages, it does not entirely follow the trajectory of the disorder, whereby depressive symptomology can often present months after exposure to stress. Furthermore, patients with depression are more likely to withdraw in response to their stressful experience, or as a symptom of their depression, and, in turn, this withdrawal/isolation can further exacerbate the stressful experience and the depressive symptomology. Therefore, we investigated the effect(s) of 6 weeks of UCMS followed by another 6 weeks of social isolation (referred to as UCMSI), on behaviour, corticosterone stress responsivity, immune system functioning, and hippocampal neurogenesis, in young adult male mice. We found that UCMSI induced several behavioural changes resembling depression but did not induce peripheral inflammation. However, UCMSI animals showed increased microglial activation in the ventral dentate gyrus (DG) of the hippocampus and astrocyte activation in both the dorsal and ventral DG, with increased GFAP-positive cell immunoreactivity, GFAP-positive cell hypertrophy and process extension, and increased s100β-positive cell density. Moreover, UCMSI animals had significantly reduced neurogenesis in the DG and reduced levels of peripheral vascular endothelial growth factor (VEGF) - a trophic factor produced by astrocytes and that stimulates neurogenesis. Finally, UCMSI mice also had normal baseline corticosterone levels but a smaller increase in corticosterone following acute stress, that is, the Porsolt Swim Test. Our work gives clinically relevant insights into the role that microglial and astrocyte functioning, and hippocampal neurogenesis may play in the context of stress, social isolation and depression, offering a potentially new avenue for therapeutic target.
10.1016/j.bbi.2020.07.015