{Reference Type}: Journal Article
{Title}: Histone deacetylase inhibition mitigates cognitive deficits and astrocyte dysfunction induced by amyloid-β (Aβ) oligomers.
{Author}: Diniz LP;Morgado J;Bergamo Araujo AP;da Silva Antônio LM;Mota-Araujo HP;de Sena Murteira Pinheiro P;Sagrillo FS;Cesar GV;Ferreira ST;Figueiredo CP;Manssour Fraga CA;Gomes FCA;
{Journal}: Br J Pharmacol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 27
{Factor}: 9.473
{DOI}: 10.1111/bph.16439
{Abstract}: <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.