During the last years several reports have demonstrated that melatonin
is a efficient free radical scavenger and general antioxidant. In add
ition, it has been shown that this neurohormone is able to increase th
e activity of glutathione peroxidase in rat brain cortex as well as th
e gene expression for some antioxidant enzymes in the Harderian gland
of female Syrian hamster. Also, it is well known that brain cells are
particularly exposed to free radicals, with antioxidant enzymes as the
major defense mechanism that the brain uses to neutralize reactive ox
ygen species. The aim of the present study was to examine the influenc
e of melatonin on gene expression for antioxidant enzymes in rat brain
cortex. Our results clearly demonstrate that exogenously administered
melatonin increases the levels of mRNA for glutathione peroxidase, co
pper-zinc superoxide dismutase, and manganese superoxide dismutase in
this tissue. These stimulatory effects are observed after both acute a
nd chronic treatment with this hormone, producing in the latter case t
he more marked increase. We therefore conclude that melatonin exerts a
n important role in providing indirect protection against free radical
injury by stimulating gene expression for antioxidant enzymes. Conseq
uently, melatonin could be considered as a potential therapeutic agent
in some age-related neurodegenerative diseases where excessive free r
adical production has been implicated.