Dataset Information

Antidepressant drugs modulate growth factors in cultured cells.

ABSTRACT:

Background

Different classes of antidepressant drugs are used as a treatment for depression by activating the catecholinergic system. In addition, depression has been associated with decrease of growth factors, which causes insufficient axonal sprouting and reduced neuronal damage repair. In this study, antidepressant treatments are analyzed in a cell culture system, to study the modulation of growth factors.

Results

We quantified the transcription of several growth factors in three cell lines after application of antidepressant drugs by real time polymerase chain reaction. Antidepressant drugs counteracted against phorbolester-induced deregulation of growth factors in PMA-differentiated neuronal SY5Y cells. We also found indications in a pilot experiment that magnetic stimulation could possibly modify BDNF in the cell culture system.

Conclusion

The antidepressant effects antidepressant drugs might be explained by selective modulation of growth factors, which subsequently affects neuronal plasticity.

SUBMITTER: Henkel AW

PROVIDER: S-EPMC2275236 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Publications

Antidepressant drugs modulate growth factors in cultured cells.

Henkel Andreas W AW Sperling Wolfgang W Rotter Andrea A Reulbach Udo U Reichardt Cornelia C Bönsch Dominikus D Maler Juan M JM Kornhuber Johannes J Wiltfang Jens J

BMC pharmacology 20080304

<h4>Background</h4>Different classes of antidepressant drugs are used as a treatment for depression by activating the catecholinergic system. In addition, depression has been associated with decrease of growth factors, which causes insufficient axonal sprouting and reduced neuronal damage repair. In this study, antidepressant treatments are analyzed in a cell culture system, to study the modulation of growth factors.<h4>Results</h4>We quantified the transcription of several growth factors in thr ...[more]

PMID: 18318898

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Project description:Elevated levels of D-2-hydroxyglutarate (D-2HG) and L-2-hydroxyglutarate (L-2HG) in the brain are associated with various pathological conditions, potentially contributing to neurological symptoms and neurodegeneration. Previous studies on animal models have revealed their capability to interfere with several cellular processes, including mitochondrial metabolism. Both enantiomers competitively inhibit the enzymatic activity of 2-oxoglutarate-dependent dioxygenases. These enzymes also execute several signaling cascades and regulate the level of covalent modifications on nucleic acids or proteins, e.g., methylation, hydroxylation, or ubiquitination, with an effect on epigenetic regulation of gene expression, protein stability, and intracellular signaling. To investigate the potential impact of 2HG enantiomers on human neuronal cells, we utilized the SH-SY5Y human neuroblastoma cell line as a model. We employed proton nuclear magnetic resonance (1H-NMR) spectroscopy of culture media that provided high-resolution insights into the changes in the content of metabolites. Concurrently, we performed biochemical assays to complement the 1H-NMR findings and to estimate the activities of lactate and 3-hydroxybutyrate dehydrogenases. Our results reveal that both 2HG enantiomers can influence the cellular metabolism of human neuroblastoma cells on multiple levels. Specifically, both enantiomers of 2HG comparably stimulate anaerobic metabolism of glucose and inhibit the uptake of several essential amino acids from the culture media. In this respect, both 2HG enantiomers decreased the catabolism capability of cells to incorporate the leucine-derived carbon atoms into their metabolism and to generate the ketone bodies. These results provide evidence that both enantiomers of 2HG have the potential to influence the metabolic and molecular aspects of human cells. Furthermore, we may propose that increased levels of 2HG enantiomers in the brain parenchyma may alter brain metabolism features, potentially contributing to the etiology of neurological symptoms in patients.

Dataset Information

Antidepressant drugs modulate growth factors in cultured cells.

Background

Results

Conclusion

Publications

Antidepressant drugs modulate growth factors in cultured cells.

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