Investigation of Phospholipid Differences in Valproic Acid-Induced Autistic Mouse Model Brain Using Mass Spectrometry Imaging

Metabolites. 2023 Jan 25;13(2):178. doi: 10.3390/metabo13020178.

Abstract

Autism is a neurodevelopmental disorder for which the cause and treatment have yet not been determined. The polyunsaturated fatty acid (PUFA) levels change rapidly in the blood or cerebrospinal fluid of autistic children and PUFAs are closely related to autism spectrum disorder (ASD). This finding suggests that changes in lipid metabolism are associated with ASD and result in an altered distribution of phospholipids in cell membranes. To further understand ASD, it is necessary to analyze phospholipids in organs consisting of nerve cells, such as the brain. In this study, we investigated the phospholipid distribution in the brain tissue of valproic acid-induced autistic mice using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Phospholipids including phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine were identified in each brain region and exhibited differences between the ASD and control groups. These phospholipids contain docosahexaenoic acid and arachidonic acid, which are important PUFAs for cell signaling and brain growth. We expect that the differences in phospholipids identified in the brain tissue of the ASD model with MALDI-MSI, in conjunction with conventional biological fluid analysis, will help to better understand changes in lipid metabolism in ASD.

Keywords: MALDI; autism spectrum disorder; mass spectrometry imaging; mouse brain; phospholipid; valproic acid.

Grants and funding

This research was supported by the Development of Measurement Standards and Technology for Biomaterials and Medical Convergence (KRISS-2022-GP2022-0006) from the Korea Research Institute of Standards and Science and Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health and Welfare, Ministry of Food and Drug Safety (KMDF_PR_20200901_0024).