Distinct behavioural and neurovascular signatures induced by acute and chronic stress in rats

Abstract

Stress is a contributing factor for several mood disorders, including depression and anxiety which are associated with significant changes in behavioural and cellular domains. Additionally, sex differences in the prevalence of these neuropsychiatric disorders are well established. Emerging evidence suggests that stress is linked to cerebrovascular diseases and that blood-brain barrier (BBB) dysfunction contributes to the development and exacerbation of neuropathology and neuroinflammation. Despite these interesting findings, very little attention has been given to the effect of both acute and chronic stress (unpredictable chronic mild stress-uCMS) on the link between behavioural and BBB alterations. In this study we used the open field and forced swimming tests (FST) to evaluate locomotor activity, anxiety- and depressive-like behaviours in male and female Wistar rats. Western blotting or ELISA were used to quantify the levels of different proteins related to BBB components and neuroinflammation in the prefrontal cortex. We found that acute stress induced anxiety only in males, whereas uCMS had no effect. Additionally, acute stress decreased immobility time in the FST pointing to a coping strategy in both sexes. In contrast, uCMS increased immobility time only in males, indicating depressive-like behaviour. Additionally, both types of stress had no major impact on TNF-α, GFAP and C3/C3aR proteins. Nevertheless, acute stress significantly reduced occludin and VEGF protein levels in both sexes, highlighting significant alterations in the neurovasculature. Concerning uCMS, there was an upregulation in claudin-5 protein levels only in females suggesting a possible compensatory mechanism of the BBB in response to a prolonged situation of stress. In conclusion, acute and uCMS induce distinct behavioural and biochemical profiles, particularly affecting BBB proteins.

Keywords: Acute stress; Behaviour; Blood-brain barrier; Neuroinflammation; Unpredictable chronic mild stress.