Melatonin Attenuates Cerebral Ischemia/Reperfusion Injury Through Suppressing Apoptosis and Inducing Autophagy

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Yılmaz Ü., Tanbek K., Gül M., Koç A., Sandal S.

NEUROENDOCRINOLOGY, cilt.1, sa.1, ss.1-10, 2023 (SCI-Expanded)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1 Sayı: 1
  • Basım Tarihi: 2023
  • Dergi Adı: NEUROENDOCRINOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1-10
  • İnönü Üniversitesi Adresli: Evet

Özet

Abstract

Aim: 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.

Material and Method: 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 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. In addition, reflections of the melatonin treatment started to show on neurological tests from the 5th day.

                                                                                       

Keywords: Cerebral ischemia, autophagy, melatonin, neurological deficit score, rotarod test, adhesive removal test