Altered IMPA2 gene expression and calcium homeostasis in bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Bipolar I disorder (BD-I) is associated with reduced inositol monophosphatase (IMPase) activity and elevated basal intracellular calcium levels ([Ca(2+)](B)) in B lymphoblast cell lines (BLCLs).
• These cellular alterations may represent endophenotypes of BD-I.
• The phosphoinositide (PI) cycle links IMPase activity to intracellular calcium mobilization.

Purpose of the Study:

• To investigate the relationship between IMPA1 and IMPA2 gene expression and intracellular calcium levels in BLCLs from BD-I patients.
• To explore potential sex-dependent differences in IMPA2 expression in relation to calcium homeostasis in BD-I.

Main Methods:

• RT-PCR was used to quantify IMPA1 and IMPA2 mRNA levels in BLCLs from BD-I patients and healthy controls.
• BLCLs were phenotyped based on basal intracellular calcium levels ([Ca(2+)](B)).
• Postmortem temporal cortex IMPA2 mRNA levels were also analyzed.

Main Results:

• IMPA2 mRNA levels were significantly lower in BLCLs from male BD-I patients with high [Ca(2+)](B) compared to controls and BD-I patients with normal [Ca(2+)](B).
• A negative correlation between IMPA2 mRNA levels and [Ca(2+)](B) was observed in male BD-I patients.
• Postmortem temporal cortex IMPA2 mRNA levels were higher in male BD-I subjects than in male controls.

Conclusions:

• These findings suggest a potential sex-dependent link between IMPA2 gene expression abnormalities and calcium homeostasis in the pathophysiology of bipolar disorder.
• IMPA2 dysregulation may contribute to cellular endophenotypes observed in BD-I.