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FC gamma receptor activation is related to neuronal and microglial toxicity mediated by palmitic acid
Author(s) -
Phitthayaphong Phansa,
Kumfu Sirinart,
Chattipakorn Siriporn C.,
Chattipakorn Nipon
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.040156
Subject(s) - proinflammatory cytokine , neuroinflammation , microglia , receptor , downregulation and upregulation , chemistry , microbiology and biotechnology , tumor necrosis factor alpha , viability assay , cell culture , endocrinology , medicine , biology , biochemistry , cell , inflammation , genetics , gene
Background A high‐fat diet (HFD) rich in saturated fatty acid, particularly palmitic acid (PA), promotes pathophysiological changes in the brain. HFD induces cognitive impairment due to abnormal Alzheimer’s‐related protein production and increases the upregulation of hyperphosphorylation of Tau and Aβ peptides. Moreover, the progression of neuroinflammation and activated microglia were driven after HFD consumption. Activated microglia are able to eliminate abnormal proteins by using surface receptors called FcγR. These receptors have been found to mediate tissue injury within the CNS. However, the expression and activation of FcγRs, the presence of Alzheimer’s‐related proteins, proinflammatory cytokines as well as cell viability of neurons and microglia under PA exposure have not been investigated. Method SH‐SY5Y, the human neuroblastoma cell line, and HMC3, the human microglia clone 3 cell line, were exposed to 200 and 400 µM of PA‐conjugated BSA. After 24 hours of exposure, Alzheimer’s‐related proteins, including Aβ, APP, BACE1, IDE, p‐Tau and Tau, as well as the production of proinflammatory cytokines composed of TNFα, IL‐1β and IL‐6, were investigated. FcγRs levels with signaling and cell viability were determined. Result After exposure of PA‐conjugated BSA for 24 hours, SH‐SY5Y and HMC3 cells increased Alzheimer’s‐related protein production including Aβ, APP, BACE1, and decreased IDE. While p‐Tau/Tau ratio was increased only in SH‐SY5Y cells. Furthermore, both cell lines increased TNFα, IL‐1β and IL‐6 production after PA‐conjugated BSA exposure. Interestingly, an increase in FcγRs expression was only found in HMC3 cells, whereas FcγRs signaling significantly increased in both cell lines. The viability of SH‐SY5Y and HMC3 cells were decreased in a dose‐dependent manner with PA exposure. Conclusion PA increased Alzheimer’s‐related protein production, inflammation and FcγRs activation, which related to the presence of neuronal and microglial cell death. These findings suggest that the blockage of FcγRs should restrain further progression of Alzheimer’s pathology and neuroinflammation in HFD‐induced cognitive decline.