Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury through Inducing Autophagy

Abstract

Introduction: The aim of this study was to investigate how melatonin administration for 3 days or 7 days following cerebral ischemia injury (CI/R) would affect autophagy, and therefore, survival in neurons of the penumbra region. Moreover, it was also aimed to determine how this melatonin treatment would affect the neurological deficit score and rotarod and adhesive removal test durations. Methods: Focal CI (90 min) was achieved in a total of 105 rats utilizing a middle cerebral artery occlusion model. After the start of reperfusion, the groups were treated with melatonin (10 mg/kg/day) for 3-days or 7-days. On all groups, neurological deficit scoring, rotarod and adhesive removal test were executed during reperfusion. Infarct areas were determined by TTC (2,3,5-triphenyltetrazolium chloride) staining at the end of the 3rd and 7th days of reperfusion. Beclin-1, LC3, p62 and caspase-3 protein levels were assessed using Western blot and immunofluorescence methods in the brain tissues. Moreover, penumbra areas were evaluated by transmission electron microscopy (TEM). Results: Following CI, it was observed that melatonin treatment improved the rotarod and adhesive removal test durations from day 5 and reduced the infarct area after CI. It also induced autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. According to TEM findings, melatonin treatment partially reduced the damage in neurons after CI. Conclusion: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3 and p62 via inhibiting the apoptotic caspase-3 protein. The functional reflection of melatonin treatment on neurological tests scores was became significant from the 5th day onward.

A study on the mechanism of Beclin-1 m6A modification mediated by catalpol in protection against neuronal injury and autophagy following cerebral ischemia

“…Beclin-1 is regarded as a major regulator of autophagy, which playing a fatal role in human neurodegenerative diseases, including cerebral ischemia (Mo et al 2020 ; Xu and Qin 2019 ). Increasing evidence showed that autophagy can be evaluated by detecting Beclin-1, LC3 and p62 expression (Yang et al 2021a , b ; Yilmaz et al 2023 ). According to our results, CAT treatment alleviated neuronal injury, decreased MCAO or OGD/R-induced Beclin-1 expression and LC3II/I ratio, and increased p62 level, while Beclin-1 overexpression nullified the protection of CAT in OGD/R-induced RN-c cells.…”

Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis

“…Protein bands were calculated with GeneTools software (Version 4.03.05, Sygene, Cambridge, UK). 22 , 30 Finally, to include representative Western blot images of the groups in the article, one rat brain tissue from each group was selected and run in gel for Beclin‐1, LC3, p62, caspase‐3 and β‐actin genes. Therefore, in the article, there is the same β‐actin gel image below the gel images of Beclin‐1, LC3, p62 and caspase‐3 genes.…”

Melatonin Inhibits Hypoxia-Induced Alzheimer’s Disease Pathogenesis by Regulating the Amyloidogenic Pathway in Human Neuroblastoma Cells

“…Previous studies have shown that melatonin inhibits Aβ-induced oxidative stress and cell death in neuronal cells [31][32][33]. Melatonin, a versatile compound, has exhibited neuroprotective effects in both in vitro and in vivo cerebral ischemia/reperfusion (I/R) models [34]. Our previous study showed that melatonin could reduce BACE1 expression in SH-SY5Y cells under normoxic conditions [35].…”