The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes

Abstract

Recently, melatonin was found to be the most potent physiological free radical scavenger known to date. In this work, we attempted to define the role this neurohormone plays in the regulation of apoptosis, since the effect of bcl-2, the main gene implicated in its inhibition, acts via an antioxidant mechanism. We investigated the role of melatonin in cell death of thymus, a well known model for the study of apoptosis. Two sets of experiments were carried out: in vivo experiments, performed with Wistar rats, and in vitro experiments, performed with primary cultures of young Wistar rat thymocytes treated with glucocorticoids in order to induce apoptosis. Morphometrical studies in semithin sections of thymus and analysis of DNA fragmentation by gel electrophoresis show that physiological apoptosis occurring in thymus of 65 days old rats, is prevented by the daily administration of melatonin beginning when the rats were 25 days old. Also, we found that at a concentration of 10(-7) M, melatonin decreases by 35% the percentage of apoptotic cells induced by glucocorticoids in cultured thymocytes of 25 day old rats. 10(-9) M melatonin decreases cell death by 20%. Finally, melatonin at 10(-11) M did not have any effect. Several hypothesis are discussed to explain this effect: direct interaction of melatonin with glucocorticoid receptors in the thymus; induction of interleukin-4 release; direct genomic action modulating the expression of apoptosis-inhibiting genes; an effect on nitric oxide synthase; and finally, the antioxidant action of melatonin. Since apoptosis is a possible mechanism involved in neuronal death shown in several neurodegenerative diseases such as Parkinson or Alzheimer's diseases, investigative efforts should be directed to the possible role of melatonin in inhibiting cell death in tissues other that the thymus. Melatonin might be a potent therapeutic agent in some of these conditions.

Effects of Exogenous Melatonin—A Review

“…It was shown that low doses of melatonin (10 −7 -10 −9 M) inhibit apoptosis in both dexamethasone-treated cultured thymocytes and the intact thymus (140). This effect of melatonin was mediated by its inhibitory influence on the proliferation of thymocytes (141).…”

Melatonin influence on Drosophila melanogaster life span at different light regimes

“…По-видимому, у млекопи-тающих он участвует в регуляции процессов старения. Например, длитель-ное введение мелатонина старым мышам замедляет возрастзависимую ин-волюцию тимуса и дегенерацию желтого пятна (Sainz et al, 1995;Yi et al, 2005). Известно, что при старении организма млекопитающих наблюда-ется постепенное снижение биосинтеза мелатонина, что является следс-твием уменьшения адренергической иннервации и количества β-адренер-гических рецепторов на поверхности пинеалоцитов (Pappolla et al, 1997).…”

Effect of Glucocorticoid and Melatonin on Immune Function of an Indian Tropical Bird, Perdicula Asiatica: An in Vivo and in Vitro Study

“…Morphometrically significant increase was noted in % apoptosis after dexamethasone supplementation whereas melatonin significantly decreased the % apoptosis of splenocytes in P. asiatica. The precise mechanism by which melatonin treatment maintains the splenic cellularity is still unknown for birds (21); melatonin might be able to prevent apoptosis and hence, maintain morphological features of lymphoid organs as noted in mammals (22) .…”