Altered purinergic receptor expression in the frontal cortex in schizophrenia

Area of Science:

• Neuroscience
• Molecular Biology
• Psychiatry

Background:

• Adenosine triphosphate (ATP) acts as a neurotransmitter via purinergic P2 receptors.
• Schizophrenia (SCZ) involves dysregulated ATP metabolism and adenosine pathways.
• The impact of altered ATP on P2 receptor expression in SCZ brains remains unclear.

Purpose of the Study:

• To investigate P2 receptor mRNA and protein expression in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in SCZ.
• To determine if altered ATP availability affects P2 receptor expression in SCZ.

Main Methods:

• Assayed P2 receptor mRNA and protein expression in DLPFC and ACC.
• Compared expression levels between SCZ subjects and matched controls (n=20-22/group).
• Analyzed correlations between P2 receptor expression, antipsychotic medication, and inflammatory markers.

Main Results:

• Significantly increased P2RX7, P2RX4, and male P2RX5 mRNA expression in the DLPFC of SCZ subjects (p < 0.05).
• Significantly increased P2RX7 protein isoform expression in the DLPFC of SCZ subjects (p < 0.05).
• P2RX4 and P2RX7 mRNA levels correlated with the inflammatory marker SERPINA3.

Conclusions:

• Brain-region-dependent dysregulation of the purinergic system occurs in SCZ.
• Upregulated P2X receptors (P2RX4, P2RX7) may be associated with neuroinflammation in SCZ.
• Antipsychotic medication effects may influence P2RX4 and male P2RX5 mRNA expression.