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Fluoxetin upregulates connexin 43 expression in astrocyte.

Mostafavi H, Khaksarian M, Joghataei MT, Hassanzadeh G, Soleimani M, Eftekhari S, Soleimani M, Mousavizadeh K, Hadjighassem MR - Basic Clin Neurosci (2014)

Bottom Line: Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects.In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients.It seems that cAMP involvement in fluoxetine effects need more researches.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran ; Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran ; Stem Cell Technology Research Center, Molecular Biology and Genetic Engineering Department, Tehran, Iran ; Department of Physiology and Pharmacology, Zanjan University of Medical Sciences, Zanjan, Iran.

ABSTRACT

Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS). Molecular target therapy studies in MS have revealed that connexin-43 (Cx43) and Aquaporin-4 (AQP4) contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.

Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 µg/ml) with or without adenyl cyclase (AC) and protein kinase A (PKA) inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.

Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.

Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

No MeSH data available.


Related in: MedlinePlus

Fluoxetine effects on AQP4 mRNA expression with and without cAMP-PKA signaling pathway. U87MG cells treated with F (Fluoxetine), SF (AC inhibitor+ Fluoxetine) and F + H89 (Fluoxetine + PKA inhibitor) for 24 hours and changes in transcript amount expression were determined by real-time qPCR. There were no significant differences in treated groups in compared to untreated controls.
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Figure 0004: Fluoxetine effects on AQP4 mRNA expression with and without cAMP-PKA signaling pathway. U87MG cells treated with F (Fluoxetine), SF (AC inhibitor+ Fluoxetine) and F + H89 (Fluoxetine + PKA inhibitor) for 24 hours and changes in transcript amount expression were determined by real-time qPCR. There were no significant differences in treated groups in compared to untreated controls.

Mentions: We reported in our previous study (not published yet) that AQP4 was not expressed in 1321N1 cells using RT-PCR and real time PCR. So we used U87MG glioma cells to study fluoxetine possible effect on AQP4 expression in this cell line. In U87MG cells, although 24 hours treatment with fluoxetine (10 and 20 µg/ml) decreased AQP4 expression, but this effect was not significant. Pretreatment of cells with AC inhibitor and PKA inhibitor had no effect on AQP4 expression level (Fig. 4). These data suggested that expression of AQP4 in this cell line have other regulatory pathway.


Fluoxetin upregulates connexin 43 expression in astrocyte.

Mostafavi H, Khaksarian M, Joghataei MT, Hassanzadeh G, Soleimani M, Eftekhari S, Soleimani M, Mousavizadeh K, Hadjighassem MR - Basic Clin Neurosci (2014)

Fluoxetine effects on AQP4 mRNA expression with and without cAMP-PKA signaling pathway. U87MG cells treated with F (Fluoxetine), SF (AC inhibitor+ Fluoxetine) and F + H89 (Fluoxetine + PKA inhibitor) for 24 hours and changes in transcript amount expression were determined by real-time qPCR. There were no significant differences in treated groups in compared to untreated controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202606&req=5

Figure 0004: Fluoxetine effects on AQP4 mRNA expression with and without cAMP-PKA signaling pathway. U87MG cells treated with F (Fluoxetine), SF (AC inhibitor+ Fluoxetine) and F + H89 (Fluoxetine + PKA inhibitor) for 24 hours and changes in transcript amount expression were determined by real-time qPCR. There were no significant differences in treated groups in compared to untreated controls.
Mentions: We reported in our previous study (not published yet) that AQP4 was not expressed in 1321N1 cells using RT-PCR and real time PCR. So we used U87MG glioma cells to study fluoxetine possible effect on AQP4 expression in this cell line. In U87MG cells, although 24 hours treatment with fluoxetine (10 and 20 µg/ml) decreased AQP4 expression, but this effect was not significant. Pretreatment of cells with AC inhibitor and PKA inhibitor had no effect on AQP4 expression level (Fig. 4). These data suggested that expression of AQP4 in this cell line have other regulatory pathway.

Bottom Line: Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects.In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients.It seems that cAMP involvement in fluoxetine effects need more researches.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran ; Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran ; Stem Cell Technology Research Center, Molecular Biology and Genetic Engineering Department, Tehran, Iran ; Department of Physiology and Pharmacology, Zanjan University of Medical Sciences, Zanjan, Iran.

ABSTRACT

Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS). Molecular target therapy studies in MS have revealed that connexin-43 (Cx43) and Aquaporin-4 (AQP4) contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.

Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 µg/ml) with or without adenyl cyclase (AC) and protein kinase A (PKA) inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.

Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.

Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

No MeSH data available.


Related in: MedlinePlus