Novel Somatostatin Receptor Subtype-4 Agonist Mitigates Microglia Inflammatory Activation

This research evaluated the impact of novel somatostatin receptor subtype-4 (SSTR4) agonist SM-I-26 on microglia inflammatory activation. SSTR4 shows particular promise as a treatment target for Alzheimer’s disease (AD) given its microglia and neuronal localization in the brain. A hallmark of AD progression is microgliosis, associated with inflammatory activation. A SSTR4 agonist that lessens microglial inflammatory activity could help mitigate AD progression. The selective and high affinity SSTR4 agonist SM-I-26 (Ki: 12nM, EC50: 17nM) was evaluated in BV2 microglia cells concurrent with inflammatory activation via lipopolysaccharide (LPS) treatment. After plating for 24hrs, cells were treated for 24hrs with SM-I-26 (0, 10, 1000nM) against LPS (0, 10, 100ng/mL). Nitrite (surrogate of nitric oxide, Griess assay) output in media and mRNA expression (RT-qPCR) from cells of key inflammatory species (Tnf-α, Il-6, Il-1β) were measured. Two-way ANOVAs with Tukey post-hoc tests were used to determine significance...