Dysfunctional microRNA-144-3p/ZBTB20/ERK/CREB1 signalling pathway is associated with MK-801-induced...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Schizophrenia is a severe mental disorder impacting brain development.
• ZBTB20 is crucial for neural development; its dysfunction is linked to neurological disorders.
• ERK/CREB signaling is a potential downstream pathway of ZBTB20, and miR-144-3p is upregulated in schizophrenia models.

Purpose of the Study:

• To investigate the association between suppressed ZBTB20/ERK/CREB1 signaling, driven by elevated miR-144-3p, and schizophrenia-like abnormalities.
• To explore the therapeutic potential of targeting the miR-144-3p/ZBTB20/ERK/CREB1 pathway in schizophrenia.

Main Methods:

• Established a MK-801 induced rat model of schizophrenia.
• Utilized RNA-Seq to identify differentially expressed genes in the hippocampus.
• Constructed miR-144-3p overexpressed cell models and assessed molecular changes via qRT-PCR, Western blots, and immunohistochemistry.
• Confirmed the interaction between miR-144-3p and ZBTB20 using bioinformatic analysis and luciferase reporter assays.

Main Results:

• RNA-Seq revealed altered ZBTB20 expression in the hippocampus of model rats.
• Reduced ZBTB20 mRNA and protein levels, alongside increased miR-144-3p, were observed in model rat brains.
• Overexpression of miR-144-3p decreased ZBTB20 expression and ERK/CREB1 phosphorylation in cell models and rat brains.
• These molecular changes were reversed by risperidone treatment.

Conclusions:

• Dysfunctional miR-144-3p/ZBTB20/ERK/CREB1 signaling is implicated in schizophrenia-like abnormalities in an animal model.
• This pathway presents a potential therapeutic target for schizophrenia treatment.