Neuroprotection by melatonin against ischemic neuronal injury associated with modulation of DNA damage and repair in the rat following a transient cerebral ischemia

Abstract

In the present study, double fluorescence staining combined with confocal laser scanning microscopy analysis were used to examine the effects of melatonin on ischemia-induced neuronal DNA strand breaks and its possible mechanisms in a transient middle cerebral artery (MCA) occlusion model. Results showed that melatonin dose-dependently reduced infarct areas and decreased both DNA double and single strand breaks (DSB and SSB) and enhanced cell viability in the peri-ischemic brain regions. Furthermore, Bcl-2 induction in the ischemic brain was further enhanced by melatonin treatment. Double staining analysis indicated that the cells costained for Bcl-2 and TdT-mediated-deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL), a DSB marker, displayed a relative regular morphology compared with the cells only stained with TUNEL. Transient ischemia induced an expression of excision repair cross-complementing factor 6 (ERCC6) mRNA, a gene essential for the preferential repair of nuclear excision repair, in the injured neurons. Double labeling showed that ERCC6 only co-localized with proliferating cell nuclear antigen (PCNA), a member of the nuclear excision repair complex, but not with TUNEL. Melatonin further and statistical significantly up-regulated ERCC6 mRNA expression in the peri-ischemic region of rat brains. The results suggest that neuroprotection by melatonin against ischemic injury may be related to modulation of apoptosis and DNA repair capacity.

Excision repair cross-complementing 1 expression protects against ischemic injury following middle cerebral artery occlusion in the rat brain

“…Melatonin has been shown to upregulate excision repair cross-complementing group 6 (ERCC6) mRNA expression in the peri-ischemic region of rat brains. 13 Vascular endothelial growth factor antisense treatment resulted in increased infarct volume and decreased ischemia-induced ERCC6 expression in the rat brain. 14,15 Moreover, IP markedly increased BER activity, whereas simultaneously reducing the nuclear accumulation of several oxidative DNA lesions following subsequent severe ischemia.…”

Effects Of Pınealectomy On Morphologıcal Features Of Blood Vessel In Chıcken: An Electron Mıcroscopıc And Stereologıcal Study

“…The pineal hormone melatonin is synthesized in the pinealocytes of the pineal gland with an endogenous rhythm and has a role in many physiological and pathological processes in human. At present, there are a number of conditions, which are said to be improved by administration of melatonin (Joo et al, 1998;Cuzzocrea et al, 2000;Sun et al, 2002;Pei et al, 2003). Recently, Pei et al, (2003) suggested that treatment with melatonin significantly reduced both the infarct volume and the brain nitric oxide production due to cerebral ischemia in rat stroke models (Anwar et al, 2001) reported that melatonin has an endothelium dependent vasorelaxant effect due to lowered calcium content in vascular tissue.…”

Melatonin for Protection Against Ionizing Radiation

“…Along this line, melatonin supplementation suppresses NO-induced apoptosis via induction of Bcl-2 expression in immortalized pineal PGT-cells (Yim et al 2002). A similar pathway of inhibitory effects of melatonin on apoptosis induced by ischemic neuronal injury has been determined (Sun et al 2002).…”