Histology-Compatible MALDI Mass Spectrometry Based Imaging of Neuronal Lipids for Subsequent Immunofluorescent Staining.
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results. We here investigated the histology compatibility of MALDI-IMS to image neuronal lipids in rodent brain tissue with subsequent immunohistochemistry and fluorescent staining of histological features. This was achieved by sublimation of a low ionization energy matrix compound, 1,5-diaminonapthalene (1,5-DAN), minimizing the number of low-energy laser shots. This yielded improved lipid spectral quality and speed of data acquisition and reduced matrix cluster formation along with preservation of specific histological information at cellular levels. This gentle, histology-compatible MALDI-IMS protocol also diminished thermal effects and mechanical stress created during nanosecond laser ablation processes that were prominent in subsequent immunofluorescent staining images but not with classical hematoxylin and eosin (H&E) staining on the same tissue section. Furthermore, this methodology proved to be a powerful strategy for investigating β-amyloid (Aβ) plaque-associated neuronal lipids as exemplified by performing high-resolution MALDI-IMS with subsequent fluorescent amyloid staining in a transgenic mouse model of Alzheimer's disease (tgSwe).
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.
Ibrahim
I
Kaya
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.
Wojciech
W
Michno
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.|Department of Chemistry and Molecular Biology, University of Gothenburg , 412 96 Gothenburg, Sweden.
Dimitri
D
Brinet
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.
Yasmine
Y
Iacone
Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital , 171 76 Stockholm, Sweden.
Giulia
G
Zanni
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , 431 80 Mölndal, Sweden.
Kaj
K
Blennow
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital , 431 80 Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London , London, WC1N 3BG, United Kingdom.
Henrik
H
Zetterberg
Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg , 431 80 Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, University College London , London, WC1N 3BG, United Kingdom.
Jörg
0000-0001-6059-198X
J
Hanrieder
D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008055:Lipids / Q000032:analysis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D016229:Amyloid beta-Peptides; D008055:Lipids