NeuropharmacologyResearch PaperLithium prevents excitotoxic cell death of motoneurons in organotypic slice cultures of spinal cord
Section snippets
Embryos and in vivo pharmacological experiments
Fertilized chicken eggs (Hy-line white) were purchased from Avigan Terralta (Vinallop, Tarragona, Catalonia, Spain) and incubated in the laboratory at 37.5 °C and 60% relative humidity. At the time of sampling, embryos were staged according to the Hamburger and Hamilton (1951) stage series. All experimental protocols used were previously approved by the Committee for Animal Care and Use of the University of Lleida.
Some embryos on embryonic day (E) 10 were treated with increasing volumes (50–600
Chronic treatment with lithium does not prevent programmed cell death of developing MNs
To investigate whether Li is able to prevent naturally occurring, caspase-dependent, apoptosis of MNs that takes place during normal avian development (Li et al., 1998, Ayala et al., 1999), Li was administered in ovo from E6 to E10, the main period of developmental cell death of lumbar MNs in the chick. This process leads to about 50% reduction of the initially differentiated MN pool (Burek and Oppenheim, 1999). Embryos were treated with different volumes (50–600 μl) of 0.15 M LiCl solution.
Discussion
In addition to the well known beneficial effects of Li for the treatment of maniac-depressive disorders, this agent has also been reported to have neuroprotective actions in distinct in vivo and in vitro paradigms in which neuronal death has been induced by excitotoxic stimuli or potassium/serum deprivation (see for review Chuang et al., 2002). In the present study, excitotoxic cell death of mature MNs was induced in an organotypic culture system of chick embryo spinal cord by exposure to KA,
Acknowledgments
We thank Imma Montoliu for technical assistance, Dr. R.W. Oppenheim for editing and comments on an earlier version of the manuscript, and Drs. Y. Uchiyama and M. Shibata for providing the anti-LC3 antibody. This work was supported by grants from the Ministerio de Ciencia y Tecnología financed jointly with FEDER (SAF2006-00619; SAF2005-01535) and the Fundació La Marató de TV3 (063030).
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