Naturwissenschaften
Dauerhafte URI für die Sektionhttps://epub.uni-luebeck.de/handle/zhb_hl/3
Listen
Auflistung Naturwissenschaften nach Schlagwort "angiogenesis"
Gerade angezeigt 1 - 1 von 1
- Treffer pro Seite
- Sortieroptionen
Item Investigation of the role of Gαq/11 signaling in brain endothelial cells(2025) Spyropoulos, DimitriosThe aging population is projected to increase in the next decades posing new challenges for societies. Normal aging can severely affect the cognitive function of individuals even in the absence of overt pathologies but currently, the therapeutic options are limited. Therefore, based on scientific evidence that aging vasculature is linked to the development of age-dependent cognitive decline, deepening our knowledge of the cerebrovascular system could unravel new potential pharmacological targets. The current study, aimed to understand the role of Gαq/11 proteins in the brain endothelium. Based on previous work, it was hypothesized that brain endothelial Gαq/11 proteins affect the cognitive function of aging mice. The hypothesis was tested with behavioral tests during the lifespan of aging mice with specific brain endothelial deletion of the genes that express the Gαq/11 proteins (Gαq/11beKO mice). The results provided evidence that the Gαq/11 proteins do not affect the memory function of young mice but have a significant effect on the cognitive function of aged mice. Immunohistological stainings on aged mice revealed increased formation of string vessels in the brains of Gαq/11beKO mice compared to control mice. String vessels are structures positive for basement membrane markers and negative for endothelial cell markers presumably resulting from collapsed vessels. Interestingly, no significant differences were found in the other parameters investigated such as neuroinflammation, neuronal and synaptic density, myelination, or blood-brain barrier (BBB) leakage. Based on literature research and previous findings of our group, shear stress was identified as a possible factor to be involved in the formation of string vessels. Mechanical stimulation of primary mouse brain endothelial cells (MPBECs) was found to induce intracellular calcium ([Ca2+]i) increase and activation of the NF-κB pathway independent from the Gαq/11 pathway. Furthermore, long-term cultivation of MPBECs under flow was identified to lead to significant morphological and proteomic changes compared to static conditions. Finally, based on the proteomic analysis, which revealed that shear stress induces angiogenic pathways in MPBECs, it was found that thrombomodulin (THBD) as well as Gαq/11 proteins are involved in in vitro migration and proliferation respectively. All in all, the current study provides evidence that the brain endothelial Gαq/11 signaling is important for cognitive function in aged mice . Future work could shed light on the exact underlying mechanisms of the observed phenotype, which could probably involve string vessel-induced hypoxia. Finally, we provide a comprehensive proteomic database that could be further exploited to unravel novel mechanosensory targets.