Melatonin attenuated the brain damage and cognitive impairment partially through MT2 melatonin receptor in mice with chronic cerebral hypoperfusion.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin | increase | cognitive function | CHP mice | - | improved | #1 |
melatonin | decrease | WM lesions | CHP mice | - | significantly improved | #2 |
melatonin | decrease | gliosis | CHP mice | - | significantly improved | #3 |
melatonin | decrease | CHP-induced brain damage | CHP mice | - | effective for | #4 |
MT2 receptor antagonist | decrease | cognitive function | CHP mice | - | reversed the improvement | #5 |
MT2 receptor antagonist | increase | WM lesion | CHP mice | - | worsened | #6 |
MT2 receptor antagonist | increase | gliosis | CHP mice | - | worsened | #7 |
BACKGROUND: Vascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model. RESULTS: The behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines. MATERIALS AND METHOD: Forty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups CONCLUSIONS: Partially through MT2 receptor, melatonin is effective for CHP-induced brain damage.