Open AccessSomatostatin Receptor Subtype-4 Regulates mRNA Expression of Amyloid-Beta Degrading Enzymes and Microglia Mediators of Phagocytosis in Brains of 3xTg-AD Mice
Author(s) -
Karin E. Sandoval,
David S. Umbaugh,
Austin House,
A. Michael Crider,
K. Witt
Publication year - 2019
Publication title -
neurochemical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.102
H-Index - 116
eISSN - 1573-6903
pISSN - 0364-3190
DOI - 10.1007/s11064-019-02890-6
Subject(s) - microglia , downregulation and upregulation , trem2 , phagocytosis , somatostatin , neprilysin , biology , receptor , medicine , inflammation , endocrinology , immunology , enzyme , biochemistry , gene
Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in memory and cognitive impairment. The use of somatostatin receptor subtype-4 (SSTR 4 ) agonists have been proposed for AD treatment. This study investigated the effects of selective SSTR 4 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 SSTR 4 as a treatment target for AD.