Four mood stabilizers commonly induce FEZ1 expression in human astrocytes.
OBJECTIVE
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.
Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan.
Zhiqian
Z
Yu
Chiaki
C
Ono
Helen B
HB
Kim
Hiroshi
H
Komatsu
Yoichiro
Y
Tanabe
Nobutaka
N
Sakae
Keiichi I
KI
Nakayama
Hiroo
H
Matsuoka
Ichiro
I
Sora
William E
WE
Bunney
Hiroaki
H
Tomita
D018692:Antimanic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D002461:Cell Line, Transformed; D016000:Cluster Analysis; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D021381:Protein Transport / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018692:Antimanic Agents; D047908:Intracellular Signaling Peptides and Proteins; C431701:LZTFL1 protein, human; D009419:Nerve Tissue Proteins; C436317:RBM14 protein, human; D014157:Transcription Factors