Quality measures of imaging mass spectrometry aids in revealing long-term striatal protein changes induced by neonatal exposure to the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA)

• Many pathological processes are not directly correlated to dramatic alterations in protein levels. The changes in local concentration of important proteins in a subset of cells or at specific loci is likely to play a significant role in the disease etiologies, but the precise location might be unknown or too small to be adequately sampled for the purpose of traditional proteomic techniques. In this respect, matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is a unique analytical method that combines analysis of multiple molecular species and their distribution in one single platform. As reproducibility is essential for successful biomarker discovery it is important to systemically assess data quality in biologically relevant MALDI IMS experiments. In the present study, we applied four simple tools to study the reproducibility for individual sections, within group variation and between group variations of data acquired from brain sections of 21 animals divided into three treatment groups. We also characterized protein changes in distinct regions of the striatum from six month-old rats treated neonatally (PND; postnatal days 9-10) with the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA) that has been implicated in neurodegenerative diseases. The results showed that optimized experimental settings can render high quality MALDI IMS data with relatively low variation (14-15 %CV) that allows characterization of subtle changes in protein expression in various subregions of the brain. This was further exemplified by the dose-dependent reduction of MBP (myelin basic protein) in the caudate putamen and the nucleus accumbens of adult rats neonatally treated with BMAA (150 and 460 mg/kg). The MBP reduction was confirmed with immunohistochemistryand indicates that developmental exposure to BMAA may induce structural effects on axonal growth and/or directly on proliferation of oligodendrocytes and myelination, which might be important for the previously shown BMAA-induced long-term cognitive impairments.

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NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

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