Blockage of Fc Gamma Receptors Alleviates Neuronal and Microglial Toxicity Induced by Palmitic Acid

Article type: Research Article

Authors: Phitthayaphong, Phansa^{a; b; c; 1} | Kumfu, Sirinart^{a; b; c; 1} | Chattipakorn, Nipon^{a; b; c} | Chattipakorn, Siriporn C.^{a; c; d; *}

Affiliations: [a] Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand | [b] Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand | [c] Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand | [d] Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

Correspondence: [*] Correspondence to: Siriporn Chattipakorn, DDS, PhD, Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Thailand. Tel.: +011 66 53 944 451; Fax: +011 66 53 222 844; E-mails: [email protected]; [email protected]

Note: [1] These authors contributed equally to this work.

Abstract: Background:Palmitic acid (PA) promotes brain pathologies including Alzheimer’s disease (AD)-related proteins, neuroinflammation, and microglial activation. The activation of neurons and microglia via their Fc gamma receptors (FcγRs) results in producing inflammatory cytokines. Objective:To investigate the expression of FcγRs, FcγR signaling proteins, AD-related proteins, proinflammatory cytokines, and cell viability of neurons and microglia in association with PA exposure as well as the effects of FcγR blockade on these parameters in response to PA. Methods:200 and 400μM PA-conjugated BSA were applied to SH-SY5Y and HMC3 cells for 24 h. For FcγR blockage experiment, both cells were exposed to FcγR blocker before receiving of 200 and 400μM of PA-conjugated BSA for 24 h. Results:PA significantly increased AD-related proteins, including Aβ and BACE1, as well as increasing TNFα, IL-1β, and IL-6 in SH-SY5Y and HMC3 cells. However, the p-Tau/Tau ratio was only increased in SH-SY5Y cells. These results were associated with an increase in FcγRs activation and a decrease in cell viability in both cell types. FcγRs blockage diminished the activation of FcγR in SH-SY5Y and HMC3 cells. Interestingly, blocking FcγRs before PA exposure reduced the increment of AD-related proteins, proinflammatory cytokines caused by PA. FcγRs blocking also inhibits cell death for 23%of SH-SY5Y cells and 64%of HMC3 cells, respectively. Conclusion:These findings suggest that PA is a risk factor for AD via the increased AD-related pathologies, inflammation, FcγRs activation, and brain cell death, while FcγR blockage can alleviate these effects.

Keywords: Alzheimer’s disease, Fc gamma receptor, microglia, neuroblastoma, obesity, palmitic acid

DOI: 10.3233/JAD-210417

Journal: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 1315-1332, 2021