%0 Journal Article
%T Histone deacetylase inhibition mitigates cognitive deficits and astrocyte dysfunction induced by amyloid-β (Aβ) oligomers.
%A Diniz LP
%A Morgado J
%A Bergamo Araujo AP
%A da Silva Antônio LM
%A Mota-Araujo HP
%A de Sena Murteira Pinheiro P
%A Sagrillo FS
%A Cesar GV
%A Ferreira ST
%A Figueiredo CP
%A Manssour Fraga CA
%A Gomes FCA
%J Br J Pharmacol
%V 0
%N 0
%D 2024 Jun 27
%M 38936407
%F 9.473
%R 10.1111/bph.16439
%X <B>OBJECTIVE: </B>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).<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.