Four mood stabilizers commonly induce FEZ1 expression in human astrocytes.

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Mood stabilizers are crucial for treating bipolar disorder.
• While their effects on neurons are known, less is understood about their impact on astrocytes.
• Previous research indicates potential glial abnormalities in bipolar disorder.

Purpose of the Study:

• To identify a common molecular response to mood stabilizers in human astrocytes.
• To investigate the role of mood stabilizers beyond neuronal effects.

Main Methods:

• Human astrocyte-derived cells (U-87 MG) were treated with lithium, valproic acid, carbamazepine, and lamotrigine.
• Microarray gene expression analysis was performed.
• Key gene findings were validated using qRT-PCR, western blot, and immunofluorescence staining.

Main Results:

• Fasciculation and elongation protein zeta 1 (FEZ1) was the sole gene consistently upregulated by all four mood stabilizers.
• FEZ1 induction was confirmed at both transcript and protein levels in astrocytes.
• FEZ1 was localized to the cytoplasm of both transformed and primary human astrocytes.

Conclusions:

• FEZ1 is likely to have significant functions within human astrocytes.
• Mood stabilizers may exert therapeutic effects, including cytoprotection, by upregulating FEZ1 expression in astrocytes.