The aim of this study was to determine the outcomes of oestrogen and
melatonin treatments following long-term ovarian
hormone depletion on
neuroinflammation and apoptotic processes in dentate gyrus of hippocampi. Forty-six female Wistar rats of 22 months of age were used. Twelve of them remained intact, and the other 34 were ovariectomized at 12 months of age. Ovariectomized animals were divided into three groups and treated for 10 weeks with oestrogens,
melatonin or saline. All rats were killed by
decapitation at 24 months of age, and dentate gyri were collected. A group of 2 month-old intact female rats was used as young control. The levels of pro-inflammatory
cytokines and
heat shock protein 70 (HSP 70) were analysed by ELISA. The expressions of TNFα, IL1β, GFAP, nNOS, iNOS, HO-1, NFκB, Bax, Bad, AIF, Bcl2 and
SIRT1 genes were detected by real-time (RT)-PCR. Western blots were used to measure the
protein expression of NFκB p65, NFκB p50/105, IκBα, IκBβ,
p38 MAPK, MAP-2 and
synapsin I. We have assessed the ability of 17β-oestradiol and
melatonin administration to downregulate markers of
neuroinflammation in the dentate gyrus of ovariectomized female rats. Results indicated that 17β-oestradiol and
melatonin treatments were able to significantly decrease expression of pro-inflammatory
cytokines, iNOS and HO-1 in the hippocampus when compared to non-treated animals. A similar age- and long-term ovarian
hormone depletion- related increase in GFAP was also attenuated after both
melatonin and
oestradiol treatments. In a similar way to
oestradiol,
melatonin decreased the activation of
p38 MAPK and NFκB pathways. The treatments enhanced the levels of synaptic molecules
synapsin I and MAP-2 and have been shown to modulate the pro-antiapoptotic ratio favouring the second and to increase
SIRT1 expression. These findings support the potential therapeutic role of
melatonin and
oestradiol as protective
anti-inflammatory agents for the central nervous system during menopause.