ArticleCNS neuroscience & therapeutics2026
Melatonin Improves Cognitive Function and Suppresses Excessive Mitophagy in Rats With Vascular Dementia.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsMelatonin has shown neuroprotective potential in various models of cerebrovascular diseases, but its effects on mitophagy in vascular dementia (VaD) induced by chronic cerebral hypoperfusion (CCH) remain unclear.
methodsEighteen adult male Sprague-Dawley rats underwent bilateral common carotid artery occlusion (BCCAO) to induce CCH. Animals were randomly assigned to three groups (n = 6 per group): sham-operated controls, BCCAO model animals receiving vehicle injection, and BCCAO animals treated with daily melatonin (10 mg/kg, intraperitoneally for 14 days). Cognitive performance was evaluated using the Morris water maze. Regional cerebral blood flow (rCBF) was measured with high-resolution laser Doppler imaging. Mitophagy was assessed via Western blot analysis of LC3BII/I, TOMM20, COX IV, caspase-3, and immunofluorescence colocalization of LC3B with TOMM20 in the hippocampal CA1 subfield.
resultsBCCAO rats exhibited significant cognitive deficits in the Morris water maze, along with persistently reduced rCBF. BCCAO also induced a significant upregulation of hippocampal mitophagy, as indicated by an elevated LC3BII/I, decreased TOMM20 and COX IV levels, and increased colocalization of TOMM20 and LC3B immunofluorescence signals. Caspase-3 expression was markedly higher in the BCCAO group. Melatonin treatment improved rCBF recovery at day 14, mitigated the spatial learning and memory impairments, decreased the LC3BII/I, increased mitochondrial protein markers (TOMM20, COX IV), reduced the colocalization of TOMM20 and LC3B puncta, and attenuated caspase-3 levels.
conclusionThese findings indicate that CCH in the VaD model induces excessive hippocampal mitophagy and cognitive impairment. The cognitive improvement observed with melatonin treatment is closely correlated with restored cerebral perfusion and attenuated mitophagic activity.
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