Neuroprotection by melatonin from glutamate‐induced excitotoxicity during development of the cerebellum in the chick embryo

Abstract

This work investigated the ability of melatonin to prevent cell damage in the cerebellar cortex of chick embryo caused by glutamate administration. Cell injury was evaluated estimating, at ultrastructural level, the phenomenon of cell death and the synaptogenesis of the Purkinje cells and the cerebellar glomerular synaptic complex. Administration of glutamate during cerebellar development of the chick provokes excitotoxic neuronal degeneration characterized by a phenomenon of neuronal cell death that exhibits essentially the features of a death pattern described as necrosis and the deletion of synaptogenic processes. Our results show that melatonin has a neuroprotective effect against glutamate-induced excitotoxicity. This effect is morphologically revealed by the lack of neural cell death in the embryos treated with melatonin prior to glutamate injection and also by the degree of a synaptogenesis similar to that exhibited by the control group. Likewise, we corroborate the absence of teratological effects of melatonin on chick cerebellar development. Although the possible mechanisms involved in the neuroprotective effect of melatonin are discussed, i.e., direct antioxidant effects, up-regulating endogenous antioxidant defenses, and inhibiting nitric oxide formation activated by glutamate, further studies are required to establish the actual mechanism involved in the neuroprotective effect of melatonin.

Possible role of pineal allopregnanolone in Purkinje cell survival

“…Although the neuroprotective action of pineal melatonin is known in birds and mammals (34,35), it has also been reported that melatonin does not fully ameliorate Purkinje cell loss during development (36). These observations suggest that certain other component(s) in the pineal gland may contribute to Purkinje cell survival during development.…”

Actions of Melatonin in the Reduction of Oxidative Stress

“…The efficiency of any agent that destroys macromolecules by processes involving free radicals should be decreased if antioxidants, including melatonin, are also present. This has been shown to be the case with melatonin; it has been effectively utilized in vitro and in vivo to combat an incredibly wide number of toxicants including peroxynitrite [22][23][24]65], indomethacin [3], alloxan [26], cisplatin [51], glutamate [29], carbon tetrachloride [62], adriamycin [60], hydrogen peroxide [96], amyloid ß protein [72,73], carrageenan [22][23][24], cerulein [83], nitrilotriacetate [82] and many others [35,87,93,99]. Melatonin has proven equally effective in reducing oxidative damage in conditions where free radical involvement has been established; such situations include ischemia/reperfusion injury [22,111], biliary obstruction [59], ionizing radiation [110], etc.…”

Accumulation of Exogenous Amyloid-BetaPeptide in Hippocampal Mitochondria Causes Their Dysfunction: A Protective Role for Melatonin

“…Melatonin is a proven antioxidant [26, 27], especially in the brain where it reduces molecular damage as demonstrated in animal models of AD [28, 29], as well as in other experimental models of neurodegeneration [30–33]. There are two important clues regarding the role of melatonin in mitochondria rescue, (1) melatonin penetrates mitochondria where it scavenges free radicals [34, 35], (2) melatonin directly inhibits mitochondrial permeability transition pore (MtPTP) [36].…”