Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats
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2024
Authors
Virijević, KristinaSpasojević, Nataša
Stefanović, Bojana
Ferizović, Harisa
Janković, Milica
Vasiljević, Perica
Dronjak, Slađana
Article (Published version)
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Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a f...urther decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD.
Keywords:
Females / Wistar Kyoto / Chronic mild stress / Depression / MAPK / PI3K/AKT signalingSource:
Neuroscience Letters, 2024, 825, 137709-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) (RS-MESTD-inst-2020-200017)
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VinčaTY - JOUR AU - Virijević, Kristina AU - Spasojević, Nataša AU - Stefanović, Bojana AU - Ferizović, Harisa AU - Janković, Milica AU - Vasiljević, Perica AU - Dronjak, Slađana PY - 2024 UR - https://vinar.vin.bg.ac.rs/handle/123456789/12934 AB - Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD. T2 - Neuroscience Letters T1 - Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats VL - 825 SP - 137709 DO - 10.1016/j.neulet.2024.137709 ER -
@article{ author = "Virijević, Kristina and Spasojević, Nataša and Stefanović, Bojana and Ferizović, Harisa and Janković, Milica and Vasiljević, Perica and Dronjak, Slađana", year = "2024", abstract = "Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD.", journal = "Neuroscience Letters", title = "Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats", volume = "825", pages = "137709", doi = "10.1016/j.neulet.2024.137709" }
Virijević, K., Spasojević, N., Stefanović, B., Ferizović, H., Janković, M., Vasiljević, P.,& Dronjak, S.. (2024). Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats. in Neuroscience Letters, 825, 137709. https://doi.org/10.1016/j.neulet.2024.137709
Virijević K, Spasojević N, Stefanović B, Ferizović H, Janković M, Vasiljević P, Dronjak S. Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats. in Neuroscience Letters. 2024;825:137709. doi:10.1016/j.neulet.2024.137709 .
Virijević, Kristina, Spasojević, Nataša, Stefanović, Bojana, Ferizović, Harisa, Janković, Milica, Vasiljević, Perica, Dronjak, Slađana, "Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats" in Neuroscience Letters, 825 (2024):137709, https://doi.org/10.1016/j.neulet.2024.137709 . .