Mapping of Fatty Aldehydes in the Diabetic Rat Brain Using On-Tissue Chemical Derivatization and Air-Flow-Assisted Desorption Electrospray Ionization-Mass Spectrometry Imaging

Abstract

Fatty aldehydes (FALs) are involved in various biological processes, and their abnormal metabolism is related to the occurrence and development of neurological diseases. Because of their low ionization efficiency, methods for in situ detection and mass spectrometry imaging (MSI) analysis of FALs remain underreported. On-tissue chemical tagging of hardly ionizable target analytes with easily ionized moieties can improve ionization efficiency and detection sensitivity in MSI experiments. In this study, an on-tissue chemical derivatization-air-flow-assisted desorption electrospray ionization-MSI method was developed to visualize FALs in the rat brain. The method showed high sensitivity and specificity, allowing the use of in situ high-resolution MS 3 to identify FALs. The methodology was applied to investigate the region-specific distribution of FALs in the brains of control and diabetic encephalopathy (DE) rats. In DE rats, FALs were found to be significantly enriched in various brain regions, especially in the cerebral cortex, hippocampus, and amygdala. Thus, increased FAL levels and oxidative stress occurred in a region-dependent manner, which may contribute to cognitive function deficits in DE. In summary, we provide a novel method for the in situ detection of FALs in biological tissues as well as new insights into the potential pathogenesis of DE.

Mobilized Electrospray Device for On-Tissue Chemical Derivatization in MALDI-MS Imaging

“…When using the recently developed METASPACE derivatization annotation tool, fatty aldehydes (FAL) are readily observed as derivatized features in the tissue. Recently, FAL in this tissue type were suggested to fluctuate between healthy individuals and those with diabetic encephalopathy, where localizations were visualized with air-flow-assisted DESI-MS imaging using GT derivatization . As shown in Figure a, there is no FAL detected without OTCD but FAL 16:0, 18:1, and 18:0 were readily detected with GT OTCD.…”

“…Recently, FAL in this tissue type were suggested to fluctuate between healthy individuals and those with diabetic encephalopathy, where localizations were visualized with air-flow-assisted DESI-MS imaging using GT derivatization. 19 As shown in Figure 9a, there is no FAL detected without OTCD but FAL 16:0, 18:1, and 18:0 were readily detected with GT OTCD. The localization of the fatty aldehydes is similar regardless of how GT is applied, but the overall signal is better when an electrospray device is used.…”