@conference{
author = "Virijević, Kristina and Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Dronjak, Slađana",
year = "2023",
abstract = "Background: The neurobiology underlying depression has not yet been fully identified, but is thought to result from molecular and cellular abnormalities that interact with genetic and environmental factors. Depression is twice as prevalent in women as in men, however, females remain underrepresented in preclinical research. In addition to the neurotransmission theory of depression, the inflammatory processes and the disrupted signaling pathways also play a crucial role in the pathophysiology of depression. The WKY rat strain has long been established as a model of depression. These rats demonstrate an exaggerated response to stress compared to other strains. WKY strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) and considered to be nonresponsive to antidepressant drugs. The hippocampus and the medial prefrontal cortex (mPFC) are thought to be an important regions for depression. Brain-derived neurotrophic factor (BDNF) play a vital role in the pathophysiology of depression. BDNF-stimulated signaling cascades, including the phosphatidylinositol 3-kinase (PI3K)–/serine threonine kinase (Akt), also implicated in depression and treatment respons. In the present study, we have examined the effects of CMS on behavior and BDNF and PI3K/Akt signaling in the hippocampus and mPFC of female WKY rats.
Method: In the experiment, we used three months old Wistar (WI) and WKY female rats. Animals were divided in two groups: control and animals exposed to CMS for 6 weeks. On the last day of stress procedure, animals were tested in elevated plus maze to determine the levels of anxiety. Animals were then sacrificed and hippocampus and mPFC were isolated. Levels of BDNF and pAkt were determined by Western blot method. Data were analyzed using the two way ANOVA and Tuckey’s post-hoc test.
Results: WKY rats showed significantly decreased number of rearings (by 70%, p<0.01),decreased number of total arm entries (by 21%, p<0.05) and the time spent in the open arms (by 73%, p<0.001) of the elevated plus-maze compared to WI control group. WKY females had a significantly lower level of BDNF in the hippocampus (by 12%, p<0.05) and mPFC (by 16%, p<0.05) and pAkt (by 14%, p<0.01) only in mPFC as compared to the WI female rats. Exposure of WKY females to CMS enhanced an anxiety-like behavior and hypolomotion (decrease in number of rearings by 31%, p<0.05, number of total arm entries by 89%, p<0.001, and timevspent in the open arms by 92%, p<0.001), further down-expression of BDNF in both brain areas (in PFC: by 15%, p<0.001; in hippocampus: by 7%, p<0.05) and Akt phosphorylation in the mPFC (by 17%, p<0.05) as well as a decreased pAkt in the hippocampus (by 36%, p<0.001).
Conclusions: The difference in the balance of BDNF and PI3K/Akt signaling pathways may be relevant to the resistance of WKY rats to antidepressant drug treatment and may be useful for developing new targets for depression treatment, especially in females.",
journal = "Neuroscience Applied",
title = "Dysregulation of BDNF and PI3K/Akt signaling in the brain of female Wistar-Kyoto rats exposed to chronic mild stress",
volume = "2",
number = "Supplement 2",
pages = "102596",
doi = "10.1016/j.nsa.2023.102596"
}
