Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Schizophrenia (SCZ) is a severe psychiatric disorder with complex pathogenesis and limited treatment efficacy.
• Inflammatory processes and galectins, involved in immune regulation and CNS homeostasis, are implicated in SCZ etiology.
• Current antipsychotic treatments are effective in only one-third of SCZ patients.

Purpose of the Study:

• To investigate the expression levels of the galectin gene family in post-mortem brain samples from SCZ patients.
• To identify potential molecular mechanisms regulating galectin expression in SCZ.
• To explore novel therapeutic targets for schizophrenia.

Main Methods:

• Quantitative analysis of galectin gene family expression in post-mortem hippocampus, striatum, and prefrontal cortex from SCZ patients and controls.
• Disease-specificity assessment by comparing SCZ with bipolar disorder and major depressive disorder (MDD) patient samples.
• Bioinformatic analyses including prediction of transcription factors, correlation with epigenetic markers, and gene ontology analysis.

Main Results:

• Significant downregulation of LGALS8 (Galectin-8) was observed in the hippocampus of SCZ patients compared to controls.
• The reduction in LGALS8 expression was specific to SCZ, with no changes noted in bipolar disorder or MDD.
• Potential regulators of LGALS8, including transcription factors (TBL1XR1, BRF2, TAF7) and microRNAs (MIR3681HG, MIR4296), were identified. No differences in LGALS8 methylation were found.
• Ontology analysis revealed enrichment of NGF-stimulated transcription and oligodendrocyte differentiation pathways associated with LGALS8 downregulation.

Conclusions:

• LGALS8 is identified as a disease-specific gene downregulated in the hippocampus of SCZ patients.
• These findings suggest LGALS8 may serve as a valuable biomarker for schizophrenia.
• Targeting LGALS8 or associated pathways presents a potential novel therapeutic strategy for schizophrenia.