Human Cerebellum Gangliosides: A Comprehensive Analysis by Ion Mobility Tandem Mass Spectrometry.
Maria Roxana BiricioiuMirela SarbuRaluca IcaŽeljka VukelićDavid E ClemmerAlina Diana ZamfirPublished in: Journal of the American Society for Mass Spectrometry (2024)
The human cerebellum is an ultraspecialized region of the brain responsible for cognitive functions and movement coordination. The fine mechanisms through which the process of aging impacts such functions are not well understood; therefore, a rigorous exploration of this brain region at the molecular level is deemed necessary. Gangliosides, sialylated glycosphingolipids, highly and specifically expressed in the human central nervous system, represent possible molecular markers of cerebellum development and aging. In this context, for a comprehensive determination of development- and age-specific components, we have conducted here a comparative profiling and structural determination of the gangliosides expressed in fetal cerebellum in two intrauterine developmental stages and aged cerebellum by ion mobility separation (IMS) mass spectrometry (MS) and tandem MS (MS/MS). Due to the high sensitivity and efficiency of separation provided by IMS MS, no less than 551 chemically distinct species were identified, which represents 4.5 times more gangliosides than ever discovered in this brain region. The detailed assessment of fetal vs aged cerebellum gangliosidome showed marked discrepancies not only in the general number of the species expressed, but also in their sialylation patterns, the modifications of the glycan core, and the composition of the ceramides. All of these characteristics are potential markers of cerebellum development and aging. The structural analysis by collision-induced dissociation (CID) documented the occurrence of GD1b (d18:1/18:0) isomer in the fetal cerebellum in the second gestational trimester, with all probability of GQ1b (t18:1/18:0) in the near-term fetus and of GQ1b (d18:1/18:0) in aged cerebellum.
Keyphrases
- mass spectrometry
- liquid chromatography
- ms ms
- endothelial cells
- tandem mass spectrometry
- multiple sclerosis
- high performance liquid chromatography
- gas chromatography
- solid phase extraction
- resting state
- induced pluripotent stem cells
- ultra high performance liquid chromatography
- high resolution
- high glucose
- pluripotent stem cells
- functional connectivity
- air pollution
- single molecule
- liquid chromatography tandem mass spectrometry
- preterm birth
- molecularly imprinted
- weight gain
- diabetic rats
- cerebrospinal fluid
- cerebral ischemia
- brain injury
- drug induced