Psychiatry Investig.  2012 Jun;9(2):180-186.

Fluoxetine Increases the Expression of NCAM140 and pCREB in Rat C6 Glioma Cells

• Choi MR
• Oh DH
• Kim SH
• Jung KH
• Das ND
• Chai YG

Abstract

OBJECTIVE
Dysfunction of neural plasticity in the brain is known to alter neural networks, resulting in depression. To understand how fluoxetine regulates molecules involved in neural plasticity, the expression levels of NCAM, NCAM140, CREB and pCREB, in rat C6 glioma cells after fluoxetine treatment were examined.
METHODS
C6 cells were cultured after 20 min or after 6, 24 or 72 h treatments with 10 microM fluoxetine. Immunocytochemistry was used to determine the effect of fluoxetine on the expression of NCAM. Western blot analysis was used to measure the expression levels of NCAM140 and CREB and the induction of pCREB after fluoxetine treatment.
RESULTS
NCAM expression following 72-h fluoxetine treatment was significantly increased around cell membranes compared to control cells. Cells treated with fluoxetine for 6 and 72 h showed a significant increase in NCAM140 expression compared to cells treated for 20 min. The level of pCREB in the cells treated with fluoxetine for 72 h not only increased more than 60%, but was also significantly different when compared with the other treatment times. The 72-h fluoxetine treatment led to the increase of NCAM140 and the phosphorylation of CREB in C6 cells.
CONCLUSION
Our findings indicate that fluoxetine treatment regulates neuronal plasticity and neurite outgrowth by phosphorylating and activating CREB via the NCAM140 homophilic interaction-induced activation of the Ras-MAPK pathway.

Keyword

Antidepressant; C6 cells; Fluoxetine; NCAM140; pCREB

MeSH Terms

Animals
Blotting, Western
Brain
Cell Membrane
Depression
Fluoxetine
Glioma
Immunohistochemistry
Neural Cell Adhesion Molecules
Neurites
Neuronal Plasticity
Phosphorylation
Plastics
Rats
Fluoxetine
Neural Cell Adhesion Molecules
Plastics