Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Tamotsu Tsukahara,Yoshikazu Matsuda,Hisao Haniu,Takeshi Uemura

doi:10.1038/s41598-020-60781-1

Tamotsu Tsukahara, Yoshikazu Matsuda + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-60781-1

Copy DOI

Abstract

Cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (PLs) from neuronal membranes. PLs are a class of amphipathic lipids that form plasma membrane lipid bilayers, and that occur at high concentrations in neuronal membranes. Our previous study suggested that a porcine liver decomposition product (PLDP) produced via protease treatment may improve cognitive function at older ages, by acting as a rich source of PLs and lysophospholipids (LPLs); however, its specific composition remains unclear. Thus, the present study used a novel liquid chromatography electrospray ionization tandem mass spectrometric (LC-MS/MS) protocol to identify the major PLs and LPLs in PLDP. Furthermore, it assessed the effect of identified LPLs on microglial activation in vitro, including cell shape, proliferation, and cell morphology. The results of the conducted analyses showed that PLDP and PLDP-derived LPLs concentration-dependently modulate microglial activation in vitro. In particular, lysophosphatidylcholine (LPC) concentration-dependently promotes cell morphology, likely via effects mediated by the enzyme autotaxin (ATX), since inhibiting ATX also promoted cell morphology, while conversely, increasing ATX production (via treatment with high levels of LPC) abolished this effect. These findings suggest that LPC is likely neuroprotective, and thus, support the importance of further research to assess its use as a therapeutic target to treat age-related cognitive impairments, including dementia.

Highlights

Cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (PLs) from neuronal membranes
We previously reported that a porcine liver decomposition product (PLDP) induces a significant increase in the Hasegawa’s Dementia Scale-Revised (HDS-R) score in a randomized, double-blind, placebo-controlled study in healthy humans[5]
The most abundant LPS detected was LPS18:0, (LPS16:0, LPS18:1, LPS18:2, LPS20:4, and LPS22:6 were detected at lower concentrations), and the most abundant lysophosphatidic acid (LPA) detected was LPA18:0

Summary

Introduction

Cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (PLs) from neuronal membranes. Lysophosphatidylcholine (LPC) concentration-dependently promotes cell morphology, likely via effects mediated by the enzyme autotaxin (ATX), since inhibiting ATX promoted cell morphology, while increasing ATX production (via treatment with high levels of LPC) abolished this effect These findings suggest that LPC is likely neuroprotective, and support the importance of further research to assess its use as a therapeutic target to treat age-related cognitive impairments, including dementia. A previous study by our research group supports the importance of further research into the potential use of PL supplementation (in PLDP) to prevent chronic and age-related disease[5]; the present study used a novel liquid chromatography electrospray ionization tandem mass spectrometric (LC-MS/MS) protocol to identify major LPLs in PLDP, and assessed the effects of identified PLDP-derived LPLs on microglial activation in vitro

Methods

Results

Discussion

Conclusion