Brain lipidomics: From functional landscape to clinical significance

Abstract

Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with the etiology and progression of neurodegeneration and other neurological pathologies. Hence, brain lipids are emerging as important potential targets for the early diagnosis and prognosis of neurological diseases. This review aims to highlight the significance and usefulness of lipidomics in diagnosing and treating brain diseases. We explored lipid alterations associated with brain diseases, paying attention to organ-specific characteristics and the functions of brain lipids. As the recent advances in brain lipidomics would have been impossible without advances in analytical techniques, we provide up-to-date information on mass spectrometric approaches and integrative analysis with other omic approaches. Last, we present the potential applications of lipidomics combined with artificial intelligence techniques and interdisciplinary collaborative research for treating brain diseases with clinical heterogeneities.

Validating MALDI-IMS Feasibility in Ex Vivo Brain Slices

“…To date, MALDI-IMS has not been employed to study ion profiles of ex vivo brain slices, in part due to the challenging requirement of handling the brain slices to extract them from their experimental setup and then section 400 μm thick brain slices down to just 10 μm without the use of an embedding material. Importantly, MALDI-IMS is uniquely equipped for lipid analysis with soft ionization and an untargeted mechanism, unlike targeted immunologic approaches. , Moreover, lipids are continuing to emerge as key players in neurologic disease and as important regulators of membrane-bound channels . Coregistration of electrophysiology and light transmittance imaging experiments in brain slices with MALDI-IMS would greatly increase our overall understanding of acute lipid changes in a variety of neuroscientific fields .…”

“…Importantly, MALDI-IMS is uniquely equipped for lipid analysis with soft ionization and an untargeted mechanism, unlike targeted immunologic approaches. , Moreover, lipids are continuing to emerge as key players in neurologic disease and as important regulators of membrane-bound channels . Coregistration of electrophysiology and light transmittance imaging experiments in brain slices with MALDI-IMS would greatly increase our overall understanding of acute lipid changes in a variety of neuroscientific fields . To achieve this, we must first validate a technique for the preparation of ex vivo brain slices for MALDI-IMS analysis.…”

Modulatory effect of n-3 polyunsaturated fatty acids on depressive-like behaviors in rats with chronic sleep deprivation: potential involvement of melatonin receptor pathway and brain lipidome

“…Polyunsaturated fatty acids (PUFA) are relevant for maintaining the neuronal structure and normal functioning of the brain. 13 They can be either consumed from food directly or synthesized by enzymatic desaturation, elongation and peroxisomal β-oxidation through nutritionally essential precursors α-linolenic acid (C18:3n-3, ALA) and linoleic acid (C18:2n-6, LA). 14 Since n-3 PUFA and n-6 PUFA compete for the same metabolic enzymes, it was reported that maintaining an optimally low n-6/n-3 PUFA ratio is linked to prevention of several diseases, such as depression.…”

Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes

“…Importantly, lipidomic analysis is becoming a valuable tool in biomedical research. It can be used to discover biomarkers for the early diagnosis and prognosis of many diseases and to understand their biological functions ( Yoon et al, 2022 ). As a result, understanding changes in lipid metabolism and their trafficking has mainly contributed to understanding the mechanisms behind various human diseases, including cancer, neurodegenerative diseases, diabetes, and obesity ( Adibhatla and Hatcher, 2008 ; Lu et al, 2014 ).…”