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BDNF‐Induced Arc Expression Was Enhanced by PIC in Neuronal Cells Treated with High Glucose and Amyloid Beta
Author(s) -
CHA HEEYUN,
Kim Se Lin,
Heo Sumin,
Park Sol Been,
Han Yeo Gyeong,
Yang Soo Jin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02563
Subject(s) - arc (geometry) , neuroprotection , brain derived neurotrophic factor , neurotrophic factors , amyloid precursor protein , tropomyosin receptor kinase b , amyloid beta , alzheimer's disease , chemistry , pi3k/akt/mtor pathway , neurofibrillary tangle , pathogenesis , amyloid (mycology) , medicine , endocrinology , microbiology and biotechnology , biology , signal transduction , receptor , pathology , disease , senile plaques , geometry , mathematics
Objectives Hyperglycemia has been shown to be associated with Alzheimer’s disease and impairment of cognitive function. Alzheimer’s disease is characterized by the excessive formation of amyloid‐beta (Aβ) and neurofibrillary tangle. Aβ is generated by cutting amyloid precursor protein (APP) by β‐secretase (BACE1) and γ‐secretase. Brain‐derived neurotrophic factor (BDNF) is the important molecule that is involved in synaptic plasticity and neuronal survival. BDNF binds to trkB receptor and activates PI3K/Akt/mTOR pathway, and it increases synaptic efficacy by inducing expression of activity‐regulated cytoskeleton‐associated protein (Arc) which is the marker of plastic changes of the brain. Suppression of BDNF is related to the pathogenesis of Alzheimer’s disease. Piceatannol (PIC) is a polyphenolic compound that has similar structure to resveratrol having neuroprotective efficacy. Thus, we investigated the effects of PIC treatment on amyloidogenesis and BDNF signaling in neuronal cells treated with high glucose and Aβ. Methods The SH‐SY5Y cells were treated with 25 mM D‐glucose and 10 μM Aβ in order to induce the cell culture model of high glucose‐induced Alzheimer’s disease. And then, cells were treated with 20 μM PIC for 24 h. Relative gene expression levels of amyloidogenesis‐ and BDNF signaling‐related markers were analyzed. Aβ concentrations were measured by ELISA to examine whether PIC alters the levels of Aβ deposit. One‐way analysis of variance (ANOVA) was performed to assign statistical significance followed by Fisher’s Least Significant Difference (LSD) post‐hoc analysis using SPSS software (IBM SPSS Statistics 24). Results In the condition of high glucose‐induced Alzheimer’s disease, PIC treatment significantly increased the relative gene expression of BACE1 ( P = 0.003). The presenilin 1 expression tended to rise up by PIC in this condition. The concentrations of Aβ were significantly lower in cells treated with high glucose, Aβ, and PIC compared with those without PIC ( P < 0.001). The relative expression levels of BDNF in high glucose group treated with PIC tended to be higher than those without PIC. PIC treatment significantly increased the relative gene expression of BDNF in cells treated with high glucose and Aβ ( P = 0.002). The Arc expression was also significantly increased by PIC in those cells ( P = 0.038). Conclusions We found that PIC improves the pathological alterations by high glucose and Aβ, which is accompanied by decreased Aβ formation and upregulation of BDNF and Arc expressions in high glucose and Aβ‐treated neuronal cells. Therefore, PIC may have a therapeutic effect on the pathological conditions of hyperglycemia‐induced Alzheimer’s disease.