5,7-dihydroxitryptamine toxicity to serotonergic neurons in serum free raphe cultures

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Joao Paulo Capela (Author) Other; Marion Lautenschlager (Author) Other; Ulrich Dirnagl (Author) Other; Maria Lourdes Bastos (Author) FFUP; Felix Carvalho (Author) FFUP; Andreas Meisel (Author) Other

Journal

Title: European Journal of Pharmacology

Vol. 588

Pages: 232-238

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 5 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-XT5

DOI: 10.1016/j.ejphar.2008.04.046

Abstract (EN): 5,7-Dihydroxytryptamine (5,7-DHT), is an experimentally widely used selective serotonergic neurotoxin, though the mechanisms of toxicity remain to be fully elucidated. In the present study, we evaluated 5,7-dihydroxitryptamine (5,7-DHT) induced serotonergic neurotoxicity in foetal raphe serum free cultures from the rat. For this purpose, a model of foetal raphe serum free neuronal cultures from the rat was established, containing about 16% serotonergic neurons and studied up to 3 months. Two weeks old raphe cultures were exposed to the serotonergic neurotoxin 5,7-DHT (concentration range 10-100 mu M) for 72 h, after which the medium was replaced and neurotoxicity was evaluated by immunocitochemistry I week later. Lactate dehydrogenase release into the medium, 72 h after exposure to 5,7-DHT, showed a concentration-dependent neurotoxicity. To access morphologically the serotonergic toxicity tryptophan hydroxylase (TPH) was used as a specific marker of these neurons. Immunocitochemistry using TPH antisera showed a concentration-dependent serotonergic neurotoxicity induced by 5,7-DHT. Serotonergic neurons showed the typical pattern of "pruning" accompanied by axon terminals and dendrites loss, which were either partial or total. The axotomy induced by the neurotoxin was morphologically characteristic of retrograde axonal degeneration. Fluoxetine (0.1 mu M) pre-treatment reduced 5,7-DHT-induced serotonergic neurotoxicity. These results indicate that the mechanism by which 5,7-DHT-induces serotonergic neurotoxicity is, at least partially, dependent on the toxin uptake by the serotonin transporter. Finally, we have established a robust model of primary raphe neuronal culture to evaluate serotonergic neurons development and the mechanisms of toxicity involving this neuronal population.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7