While stress is a natural part of life and can even be beneficial in small doses, excessive exposure, whether acute or chronic, can have profound negative effects, particularly on the brain. One of the most vulnerable targets is the blood-brain barrier (BBB), a critical structure that shields the brain from potentially harmful substances. However, the mechanisms through which different types of stress affect the BBB remain poorly understood.
A recent study led by Ana Paula Silva aimed to clarify this issue by analyzing the effects of acute and chronic stress using the unpredictable chronic mild stress (uCMS) model, in which male and female rats were exposed to alternating mild stressors over time.
The results showed that acute stress induces anxiety-like behaviors, especially in males, while chronic stress was more closely associated with depressive symptoms. Additionally, changes were observed in key BBB proteins, with significant sex-related differences. This research highlights the importance of distinguishing between types of stress and considering biological variables such as sex in neuroscience research.
Understanding these differences may be essential for developing more targeted and effective approaches to prevent and treat mental health disorders such as anxiety and depression.
This study was published in the scientific journal Behavioural Brain Research, in the article Distinct behavioural and neurovascular signatures induced by acute and chronic stress in rats, as a part of research project 73/20 - Cerebrovascular hypothesis of stress-induced behavioral alterations, supported by the BIAL Foundation.
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.
