Targeting brain and peripheral plasticity of the lipidome in acute kainic acid-induced epileptic seizures in mice via quantitative mass spectrometry

Simultaneous lipidomic and transcriptomic profiling in mouse brain punches of acute epileptic seizure model compared to controls

“…Injection of the mice (KA, 10 animals; saline, 10 animals), as well as behavioral scoring ( Fig. 1) and brain isolation, was performed as previously described (8). All collected whole brains were stored at 80°C prior to punching.…”

“…Several studies investigated the role of different molecular species in the onset and progression of epilepsy; however, multi-omic studies are mostly restricted to RNA and protein research (25,26). Recently, we found distinct lipid level alterations in six brain regions, peripheral tissues, and plasma from mice at acute epileptic seizure state induced by kainic acid (KA) (8). The involvement of lipids in the onset and progression of neurological diseases opens new venues for development of therapeutic agents, and plasma biomarker discovery for early diagnosis, prediction, and follow-up monitoring (27)(28)(29).…”

“…Interrogations in neurological diseases often require qualitative and quantitative molecular profiling at higher spatial resolution in the brain to more precisely localize the functional (sub)areas of the brain or cell populations involved in the disease. This aspect has recently also been emphasized to be of high relevance in epilepsy research (8). Brain punching is a typical procedure to enable such profiling (34).…”

“…To circumvent these limitations and expedite the targeted lipidomic and transcriptomic investigation in the brain at increased spatial resolution, we developed a method for simultaneous extraction of eCBs and arachidonic acid (AA) (collectively referred to as eCBs), PLs, and RNA from a single tissue sample obtained by brain punching. Continuing our epilepsy research (8), we then aimed at unraveling subregional lipid and mRNA fingerprints in brain punches of dorsal hippocampus (dHC), ventral hippocampus (vHC), basolateral amygdala (BLA), and hypothalamus (HYP) at acute epileptic seizure state. Combined with lipid MSI analysis, our study provides new insights into the subregional and/or cellular lipid dynamics caused by epileptic seizures.…”

Common cases of improper lipid annotation using high-resolution tandem mass spectrometry data and corresponding limitations in biological interpretation

“…Despite the proposed shorthand notation, there has been a mix of annotation styles present in literature. For example, of the lipidomics research articles published in 2017 determined on Science Direct (accessed 02/09/2017), 3 articles [29,32,33] incorrectly used “/”, 3 articles [34–36] used “-”, and1article [37] used “_” between fatty acyl constituents, when positional isomers were not identified. One potential source of confusion in annotating lipids is that current lipid identification software, for example LipidSearch, MS-DIAL [38], LipidBlast [39], and Greazy [40] all employ “/”when fatty acyl positions are not known.…”