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• W2980492026 abstract "Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in memory and cognitive impairment. The use of somatostatin receptor subtype-4 (SSTR4) agonists have been proposed for AD treatment. This study investigated the effects of selective SSTR4 agonist NNC 26-9100 on mRNA expression of key genes associated with AD pathology (microglia mediators of Aβ phagocytosis, amyloid-beta (Aβ)-degrading enzymes, anti-oxidant enzymes and pro-inflammatory cytokines) in 3xTg-AD mice. Mice were administered NNC 26-9100 (0.2 µg, i.c.v.) or vehicle control, with cortical and subcortical brain tissue collected at 6 h and 24 h post-treatment. At 6 h, NNC 26-9100 treatment decreased cortical expression of cluster of differentiation-33 (Cd33) by 25%, while increasing cortical and subcortical macrophage scavenger receptor-1 (Msr1) by 1.8 and 2.0-fold, respectively. The Cd33 downregulation and Msr1 upregulation support a state of microglia associated Aβ phagocytosis. At 24 h, NNC 26-9100 treatment increased the cortical expression of Sstr4 (4.9-fold), Aβ-degrading enzymes neprilysin (9.3-fold) and insulin degrading enzyme (14.8-fold), and the antioxidant catalase (3.6-fold). Similar effects at 24 h were found in subcortical tissue with NNC 26-9100 treatment, but did not reach statistical significance. No changes in pro-inflammatory cytokine expression were found. These data demonstrated NNC 26-9100 facilitates transcriptional changes in brain tissue identified with Aβ phagocytosis and clearance, further supporting SSTR4 as a treatment target for AD." @default.
• W2980492026 created "2019-10-25" @default.
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• W2980492026 date "2019-10-19" @default.
• W2980492026 modified "2023-10-16" @default.
• W2980492026 title "Somatostatin Receptor Subtype-4 Regulates mRNA Expression of Amyloid-Beta Degrading Enzymes and Microglia Mediators of Phagocytosis in Brains of 3xTg-AD Mice" @default.
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• W2980492026 doi "https://doi.org/10.1007/s11064-019-02890-6" @default.
• W2980492026 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6894394" @default.
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• W2980492026 hasPublicationYear "2019" @default.
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