Somatostatin Receptor Subtype-4 Regulates mRNA Expression of Amyloid-Beta Degrading Enzymes and Microglia Mediators of Phagocytosis in Brains of 3xTg-AD Mice
Autor: | Karin E. Sandoval, Albert M. Crider, Austin House, Ken A. Witt, David Umbaugh |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Amyloid beta Phagocytosis Sialic Acid Binding Ig-like Lectin 3 Aminopyridines Down-Regulation Mice Transgenic Insulysin Biochemistry Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation Alzheimer Disease Internal medicine medicine Insulin-degrading enzyme Animals RNA Messenger Receptors Somatostatin Scavenger receptor Neprilysin biology Microglia Chemistry Somatostatin receptor Thiourea Brain Scavenger Receptors Class A General Medicine Catalase Up-Regulation 030104 developmental biology Endocrinology medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery |
Zdroj: | Neurochem Res |
ISSN: | 1573-6903 0364-3190 |
Popis: | 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. |
Databáze: | OpenAIRE |
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