J Neurosci Res. 2025 Aug;103(8):e70070. doi: 10.1002/jnr.70070.

ABSTRACT

Melatonin and its receptors play a primary role in regulating circadian rhythms, which are frequently disrupted in patients with Alzheimer’s disease (AD). Furthermore, there is increasing evidence that the use of a ketogenic diet (KD) delays the onset of AD. Therefore, we aimed to investigate whether KD has an ameliorative effect on AD through the regulation of melatonin receptors. In this study, male Sprague-Dawley rats were divided into three groups: sham, AD, and KD. At the end of KD supplementation, behavioral parameters were determined by the Morris Water Maze. Melatonin levels, protein expression levels, and immunoreactivity of MT1-MT2 in thehippocampus and striatum were determined by ELISA, Western blotting, and immunofluorescence staining, respectively. As a result, KD improved memory decline in AD rats. Also, KD increased melatonin levels in the hippocampus but did not affect striatum melatonin levels. MT1 expression tended to increase in the hippocampus of the AD group, while MT2 expression decreased. On the contrary, KD treatment increased both MT1 and MT2 expressions. In the striatum, there was no change in MT1 expression in the AD and KD groups, but MT2 expression increased in the AD group compared with the sham group and was suppressed in the KD group. In addition, KD treatment reduced streptozotocin-induced apoptosis and neuroinflammation in the hippocampus and striatum. Our results suggest that KD may improve AD-associated inflammation and apoptosis by altering melatonin levels and the expression of MT2 receptors in the hippocampus and striatum. Therefore, KD may be a promising preventive and therapeutic option for AD.

PMID:40751333 | DOI:10.1002/jnr.70070

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