Related Experiment Video
Updated: May 28, 2026

Generation and Characterization of Human Induced Pluripotent Stem Cell-derived Astrocytes Lacking Fragile X Messenger Ribonucleoprotein
Published on: June 6, 2025
Four mood stabilizers commonly induce FEZ1 expression in human astrocytes
Zhiqian Yu1, Chiaki Ono, Helen B Kim
1Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Objectives:
Mood stabilizers influence the morphology, chemotaxis, and survival of neurons, which are considered to be related to the mood-stabilizing effects of these drugs. Although previous studies suggest glial abnormalities in patients with bipolar disorder and an effect of mood stabilizers on certain genes in astrocytes, less is known about the effects of mood stabilizers in astrocytes than in neurons. The present study identifies a common underlying response to mood stabilizers in astrocytes.
Methods:
Human astrocyte-derived cells (U-87 MG) were treated with the four most commonly used mood stabilizers (lithium, valproic acid, carbamazepine, and lamotrigine) and subjected to microarray gene expression analyses. The most prominently regulated genes were validated by qRT-PCR and western blot analysis. The intercellular localization of one of these regulated genes, fasciculation and elongation protein zeta 1 (FEZ1), was evaluated by immunofluorescence staining.
Results:
The microarray data indicated that FEZ1 was the only gene commonly induced by the four mood stabilizers in human astrocyte-derived cells. An independent experiment confirmed astrocytic FEZ1 induction at both the transcript and protein levels following mood stabilizer treatments. FEZ1 localized to the cytoplasm of transformed and primary astrocytes from the human adult brain.
Conclusions:
Our data suggest that FEZ1 may play important roles in human astrocytes, and that mood stabilizers might exert their cytoprotective and mood-stabilizing effects by inducing FEZ1 expression in astrocytes.
Insights
Mood stabilizers commonly induce the FEZ1 gene in human astrocytes, suggesting this protein plays a role in mood stabilization and may offer cytoprotective effects in the brain.
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.
More Related Videos
12:19Imaging Intracellular Ca2+ Signals in Striatal Astrocytes from Adult Mice Using Genetically-encoded Calcium Indicators
Published on: November 19, 2014
11:19Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)
Published on: September 26, 2015
Related Concept Videos
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
Antiepileptic Drugs: GABAergic Pathway Potentiators
The key GABA pathway potentiators used in epilepsy management are as follows.
Benzodiazepines are a well-known class of drugs used for their...
Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...
Antiepileptic Drugs: Glutamate Antagonists
Mania and Antimanic Drugs: Overview
Drugs Affecting Neurotransmitter Synthesis