Antidepressant imipramine induces human astrocytes to differentiate into cells with neuronal phenotype

• Published in: The international journal of neuropsychopharmacology 2010-06, Vol.13 (5), p.603-615
• Main Authors: Cabras, Stefano, Saba, Francesca, Reali, Camilla, Scorciapino, Maria Laura, Sirigu, Annarita, Talani, Giuseppe, Biggio, Giovanni, Sogos, Valeria
• Format: Article
• Language: English
• Subjects: Antidepressive Agents, Tricyclic - pharmacology; Astrocytes - chemistry; Astrocytes - cytology; Astrocytes - drug effects; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cells, Cultured; Fetus; Glial Fibrillary Acidic Protein - analysis; Humans; Imipramine - pharmacology; Neurogenesis - drug effects; Neurogenesis - physiology; Neurons - chemistry; Neurons - cytology; Neurons - drug effects; Phenotype; Stem Cells - chemistry; Stem Cells - cytology; Stem Cells - drug effects
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145710000210

Several recent studies have expanded our conception of the role of astrocytes in neurogenesis, proposing that these cells may contribute to this phenomenon not only as a source of trophic substances, but also as stem cells themselves. We recently observed in vitro that human mature astrocytes can be induced to differentiate into cells with a neuronal phenotype. Antidepressant drugs have been shown to increase neurogenesis in the adult rodent hippocampus. In order to better understand the role of astroglia in antidepressant-induced neurogenesis, primary astrocyte cultures were treated with the antidepressant imipramine. Cell morphology was rapidly modified by treatment. In fact, whereas untreated astrocytes showed large, flat morphology, after a few hours of treatment cells exhibited a round-shaped cell body with long, thin processes. The expression of neuronal markers was analysed by immunocytochemistry, Western Blot and RT–PCR at different treatment times. Results showed an increase in neuronal markers such as neurofilament and neuron-specific enolase (NSE), whereas glial fibrillary acidic protein (GFAP) and nestin expression were not significantly modified by treatment. Similar results were obtained with fluoxetine and venlafaxine. Hes1 mRNA significantly increased after 2 h of treatment, suggesting involvement of this transcription factor in this process. These results confirm the role of astrocytes in neurogenesis and suggest that these cells may represent one of the targets of antidepressants.