Abstract：
OBJECTIVE: Inhibitors of histone deacetylases (iHDACs) are promising drugs for neurodegenerative diseases. We have evaluated the therapeutic potential of the new iHDAC LASSBio-1911 in Aβ oligomer (AβO) toxicity models and astrocytes, key players in neuroinflammation and Alzheimer\'s disease (AD).
METHODS: Astrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice. Cognitive function was evaluated by behavioural assays using a mouse model of intracerebroventricular infusion of AβO.
RESULTS: LASSBio-1911 modulates reactivity and synaptogenic potential of cultured astrocytes and improves synaptic markers in cultured neurons and in mice. It prevents AβO-triggered astrocytic reactivity in mice and enhances the neuroprotective potential of astrocytes. LASSBio-1911 improves behavioural performance and rescues synaptic and memory function in AβO-infused mice.
CONCLUSIONS: These results contribute to unveiling the mechanisms underlying astrocyte role in AD and provide the rationale for using astrocytes as targets to new drugs for AD.
METHODS: Astrocyte phenotype and synapse density were evaluated by flow cytometry, Western blotting, immunofluorescence and qPCR, in vitro and in mice. Cognitive function was evaluated by behavioural assays using a mouse model of intracerebroventricular infusion of AβO.
RESULTS: LASSBio-1911 modulates reactivity and synaptogenic potential of cultured astrocytes and improves synaptic markers in cultured neurons and in mice. It prevents AβO-triggered astrocytic reactivity in mice and enhances the neuroprotective potential of astrocytes. LASSBio-1911 improves behavioural performance and rescues synaptic and memory function in AβO-infused mice.
CONCLUSIONS: These results contribute to unveiling the mechanisms underlying astrocyte role in AD and provide the rationale for using astrocytes as targets to new drugs for AD.
摘要：
目的：组蛋白脱乙酰酶（iHDACs）抑制剂是治疗神经退行性疾病的有前景的药物。我们已经评估了新的iHDACLASSBio-1911在Aβ寡聚体（AβO）毒性模型和星形胶质细胞中的治疗潜力，神经炎症和阿尔茨海默病(AD)的关键参与者。
方法：通过流式细胞术评估星形胶质细胞表型和突触密度，西方印迹,免疫荧光和qPCR，在体外和小鼠中。使用脑室内输注AβO的小鼠模型通过行为测定来评估认知功能。
结果：LASSBio-1911调节培养的星形胶质细胞的反应性和突触形成潜能，并改善培养的神经元和小鼠的突触标记。它可以防止AβO触发的小鼠星形胶质细胞反应性，并增强星形胶质细胞的神经保护潜力。LASSBio-1911改善AβO输注小鼠的行为表现并挽救突触和记忆功能。
结论：这些结果有助于揭示星形胶质细胞在AD中的潜在作用机制，并为使用星形胶质细胞作为AD新药的靶标提供了理论基础。
方法：通过流式细胞术评估星形胶质细胞表型和突触密度，西方印迹,免疫荧光和qPCR，在体外和小鼠中。使用脑室内输注AβO的小鼠模型通过行为测定来评估认知功能。
结果：LASSBio-1911调节培养的星形胶质细胞的反应性和突触形成潜能，并改善培养的神经元和小鼠的突触标记。它可以防止AβO触发的小鼠星形胶质细胞反应性，并增强星形胶质细胞的神经保护潜力。LASSBio-1911改善AβO输注小鼠的行为表现并挽救突触和记忆功能。
结论：这些结果有助于揭示星形胶质细胞在AD中的潜在作用机制，并为使用星形胶质细胞作为AD新药的靶标提供了理论基础。
