Comparative analysis of corpus callosum lipidome and transcriptome in schizophrenia and healthy brain

Abstract

BACKGROUND: Functional and structural studies of the brain highlight the importance of white matter alterations in schizophrenia. However, molecular studies of the alterations associated with the disease remain insufficient.

AIM: To study the lipidome and transcriptome composition of the corpus callosum in schizophrenia, including analyzing a larger number of biochemical lipid compounds and their spatial distribution in brain sections, and corpus callosum transcriptome data. To integrate the results of molecular approaches to create a comprehensive molecular perspective of the disease.

METHODS: A total of 8 brain tissue samples (4 from healthy controls (HC) + 4 from schizophrenia patients (SZ)) were analyzed using high-performance liquid chromatography with mass spectrometry (HPLC-MS) and RNA sequencing for transcriptome profiling. Additionally, 6 brain tissue samples (3 HC + 3 SZ) were analyzed using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI). This approach enabled the characterization of mRNA and lipids in brain tissue samples, and the spatial distribution of selected lipids within brain sections.

RESULTS: The analysis revealed a general trend of reduced lipid levels in the corpus callosum of schizophrenia patients for lipid classes measured by mass spectrometric methods. Specifically, nine lipid classes detected via HPLC-MS showed significant differences in schizophrenia samples, with seven of them having lower median intensity. The results between HPLC-MS and MALDI-MSI were highly concordant. Transcriptome analysis identified 1,202 differentially expressed genes, clustered into four functional modules, one of which was associated with lipid metabolism.

CONCLUSION: We identified a series of lipidome and transcriptome alterations in the corpus callosum of schizophrenia patients that were internally consistent and aligned well with previous findings on white matter lipidome changes in schizophrenia. These results add to the existing scope of molecular alterations associated with schizophrenia, shedding light on the biological processes potentially involved in its pathogenesis.

Keywords

schizophrenia / lipidomics / transcriptomics / mass spectrometry / corpus callosum

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Funding

Russian Science FoundationРоссийский Научный Фонд(20-15-00299)

Russian Science FoundationРоссийский Научный Фонд(22-15-00474)

RIGHTS & PERMISSIONS

Osetrova M.S., Efimova O.I., Zavolskova M.D., Stekolschikova E.A., Vladimirov G.N., Senko D.A., Zhuravleva T.A., Morozova A.Y., Zorkina Y.A., Andreyuk D.S., Kostyuk G.P., Nikolaev E.N., Khaitovich P.E.