MSACL 2024 Abstract

Neurotransmitters and neuropeptides are important signaling molecules in the brain and alterations in their expression levels have been linked to numerous neurological disorders, such as Parkinson’s disease (PD). Mass spectrometry imaging (MSI) can be used for the direct analysis of neurotransmitters, but has found only limited applications in the study of neurotransmitters due to their poor ionization efficiencies. Therefore, we have developed methods to image multiple neurotransmitters and neuropeptides in brain tissue sections by matrix-assisted laser desorption ionization (MALDI)-MSI at high lateral resolution.

We used ultrahigh mass resolution Fourier-transform ion cyclotron resonance (FTICR) MALDI-MSI for the comprehensive mapping of neurotransmitter networks in specific brain regions. The reactive MALDI matrix (FMP-10) facilitated the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites (1,2). Hence, it improved the detection limit toward low-abundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitters in fine structures of the brain. Furthermore, it is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Thus, we developed and evaluated a method to image multiple neuropeptides simultaneously in tissue sections (3). Furthermore, we established a spatial omics approach that combines histology, MALDI-MSI and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions (4). The workflow is compatible with commercially available Visium glass slides. The presented approach provides a further level of multimodality when studying small molecules in a tissue context. We illustrated the capabilities of the developed methods on PD brain samples from human post-mortem tissue and animal experimental models. Our approaches highlight the capacity of MALDI-MSI to elucidate the dynamics of signaling molecules in, for example, experimental PD and its treatment.

1. Shariatgorji et al., Nat Methods. 2019, 16:1021-1028. doi: 10.1038/s41592-019-0551-3
2. Shariatgorji et al., Nat Protoc. 2021, 16(7):3298-3321. doi: 10.1038/s41596-021-00538-w
3. Hulme et al., Neurobiol Dis. 2020, 137, 104738. doi: 10.1016/j.nbd.2020.104738
4. Vicari et al., Nat Biotechnol. 2023, doi: 10.1038/s41587-023-01937-y