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Mass Spectrometry Imaging Combined with Sparse Autoencoder Method Reveals Altered Phosphorylcholine Distribution in
Md Foyzur Rahman1, Ariful Islam1, Md Monirul Islam1
1Department of Cellular and Molecular Anatomy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-ku, Hamamatsu 431-3192, Shizuoka, Japan.
International Journal of Molecular Sciences
|July 27, 2024
Summary
Imipramine treatment significantly decreased phosphorylcholine (ChoP) levels in mouse brains. This finding, identified using advanced mass spectrometry imaging and sparse autoencoder analysis, highlights ChoP as a key metabolite affected by this antidepressant.
Area of Science:
- Neuroscience
- Pharmacology
- Analytical Chemistry
Background:
- Mass spectrometry imaging (MSI) is crucial for visualizing drug and metabolite distribution in pharmacokinetic studies.
- Imipramine, a tricyclic antidepressant, is known to influence endogenous metabolite concentrations.
- Understanding imipramine's impact on brain metabolites is essential for pharmacokinetic and pharmacodynamic research.
Purpose of the Study:
- To investigate the distribution and impact of imipramine on endogenous metabolites in mouse brains using AP-MALDI-MSI.
- To evaluate the effectiveness of different dimensionality reduction methods for analyzing MSI data.
- To identify potential metabolite markers affected by imipramine treatment.
Main Methods:
- Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-MALDI-MSI) was performed on brain sections from control and imipramine-treated mice.
- Dimensionality reduction techniques, including principal component analysis, multivariate curve resolution, and sparse autoencoder (SAE), were applied to the MSI data.
- SAE was utilized for peak selection and identification of distinguishing metabolites.
Main Results:
- The sparse autoencoder (SAE) method successfully identified phosphorylcholine (ChoP) as a marker differentiating between control and imipramine-treated mouse brains.
- A significant decrease in ChoP accumulation was observed in multiple brain regions of imipramine-treated mice, including the cerebellum, hypothalamus, thalamus, midbrain, caudate putamen, and ventral striatum.
- The study demonstrated the utility of SAE for peak selection in AP-MALDI-MSI data analysis.
Conclusions:
- The sparse autoencoder (SAE) method is a novel and effective approach for peak selection in AP-MALDI-MSI data.
- Imipramine treatment leads to a significant reduction in phosphorylcholine (ChoP) levels in specific regions of the mouse brain.
- This study provides valuable insights into the metabolic effects of imipramine and showcases advanced analytical techniques for neurochemical research.
