Expression analysis of actin-related genes as an underlying mechanism for mood disorders.
In this study, we explored the newly postulated 'disturbed cytoskeletal' theory of mood disorders. Firstly, we identified Cap1, a gene for important mediator of actin turnover, as a cogent quantitative trait gene for depressive trait of mice by combining the results of our prior genetic and current genome-wide expression analyses. Then we rigorously examined 'core' actin-related gene expression in the frontal cortex of C57BL/6 (B6) (prone to depression) and C3H/He (C3) (resistant to depression) mice. We confirmed that Cap1 was down-regulated at both transcript and protein levels in B6. Other differentially regulated genes included cofilin1 and profilin1 (up-regulated in B6), and a Rho-family GTPase member (Pak1) (down-regulated in B6). Thirdly, we investigated the 'core' actin-pathway components in human postmortem prefrontal cortices, and observed trend for CAP1 reduction in the bipolar brains. These data suggest that the balance of actin dynamics might be altered towards actin depolymerization in mood disorders.
Nakatani
Noriaki
N
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
Ohnishi
Tetsuo
T
Iwamoto
Kazuya
K
Watanabe
Akiko
A
Iwayama
Yoshimi
Y
Yamashita
Shunji
S
Ishitsuka
Yuichi
Y
Moriyama
Kenji
K
Nakajima
Mizuho
M
Tatebayashi
Yoshitaka
Y
Akiyama
Haruhiko
H
Higuchi
Teruhiko
T
Kato
Tadafumi
T
Yoshikawa
Takeo
T
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D051338:Cofilin 1 / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D051379:Mice; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism*; D051304:Profilins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013045:Species Specificity; D054462:p21-Activated Kinases
D000199:Actins; C489549:CAP1 protein, human; D018797:Cell Cycle Proteins; D051338:Cofilin 1; D003598:Cytoskeletal Proteins; C495738:PFN1 protein, human; D051304:Profilins; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases