New insights on targeting extracellular vesicle release by GW4869 to modulate lipopolysaccharide-induced neuroinflammation in mice model.

Autor:	Liu X; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China., Meng P; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China.; Lon-EV Biotechnology Limited Company, West Cloud Valley, Fengxi New Town, Xixian District, Xi'an 710054, China., Liu Z; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China., Tian X; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China., Xi J; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China.; College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China., Du M; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China.; College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China., Yang H; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China., Long Q; Department of Neurosurgery, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5a Road, Xincheng District, Xi'an, 710003, P.R. China.; Mini-invasive Neurosurgery & Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University. No. 161, West 5b Road, Xincheng District, Xi'an, 710003, P.R. China.; College of Medicine, Yan'an University, Yongxiang Road, Baota District, Yan'an, 716000, China.
Jazyk:	angličtina
Zdroj:	Nanomedicine (London, England) [Nanomedicine (Lond)] 2024 Nov 21, pp. 1-14. Date of Electronic Publication: 2024 Nov 21.
DOI:	10.1080/17435889.2024.2422811
Abstrakt:	Aim: This study aims to elucidate the regulatory role of extracellular vesicle (EV) release in glial cell activation, microglia-astrocyte interactions and neurological outcomes. Materials & methods: We employed a pharmacological intervention using GW4869 to modulate EV release, investigating its impact on primary cultures of microglia and astrocytes, microglia-astrocyte interactions, neuroinflammation and behavioral changes in lipopolysaccharide (LPS)-induced cell and animal models. Results: We isolated the EVs from glial cells and confirmed their positivity for CD9, CD63 and CD81. Our findings demonstrate that GW4869 significantly reduced EV protein concentrations secreted by glial cells within 6-12 h. Utilizing ELISA, immunostaining and western blot analyses, we observed that treatment with GW4869 attenuated glial cell activation and inflammatory responses both in vitro and in vivo . Transwell assays indicated that controlled EV release from activated microglia and astrocytes mitigated neurotoxic reactivity in normal astrocytes and microglia, respectively. Furthermore, GW4869 administration in LPS-injected mice resulted in notable improvements in spatial memory, anxiety-like behaviors and exploratory activity compared with vehicles. Conclusion: Our study suggests that modulating glia-derived EV dynamics effectively reduce neuroinflammation and enhance behavioral outcomes in mice. These findings underscore the potential of targeting EV release as a novel therapeutic approach for neurological disorders.
Databáze:	MEDLINE
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