Background: Brain amyloid deposition and neurofibrillary tangles in Alzheimer's disease (AD) are associated with complex neuroinflammatory reactions such as microglial activation and cytokine production. Glucose metabolism is closely related to neuroinflammation. Ketogenic diets (KDs) include a high amount of fat, low carbohydrate and medium-chain triglyceride (MCT) intake. KDs lead to the production of ketone bodies to fuel the brain, in the absence of glucose. These nutritional interventions are validated treatments of pharmacoresistant epilepsy, consequently leading to a better intellectual development in epileptic children. In neurodegenerative diseases and cognitive decline, potential benefits of KD were previously pointed out, but the published evidence remains scarce. The main objective of this review was to critically examine the evidence regarding KD or MCT intake effects both in AD and ageing animal models and in humans. Main body: We conducted a review based on a systematic search of interventional trials published from January 2000 to March 2019 found on MEDLINE and Cochrane databases. Overall, 11 animal and 11 human studies were included in the present review. In preclinical studies, this review revealed an improvement of cognition and motor function in AD mouse model and ageing animals. However, the KD and ketone supplementation were also associated with significant weight loss. In human studies, most of the published articles showed a significant improvement of cognitive outcomes (global cognition, memory and executive functions) with ketone supplementation or KD, regardless of the severity of cognitive impairments previously detected. Both interventions seemed acceptable and efficient to achieve ketosis. Conclusion: The KD or MCT intake might be promising ways to alter cognitive symptoms in AD, especially at the prodromal stage of the disease. The need for efficient disease-modifying strategies suggests to pursue further KD interventional studies to assess the efficacy, the adherence to this diet and the potential adverse effects of these nutritional approaches.
Preterm infants born before 29 gestation weeks incur major risk of subependymal/intracerebral/intraventricular hemorrhage. In mice, neonate brain endothelial cells are more prone than adult cells to secrete proteases under glutamate challenge, and invalidation of the Serpine 1 gene is accompanied by high brain hemorrhage risk up to five days after birth. We hypothesized that the structural and functional states of microvessels might account for age-dependent vulnerability in mice up to five days after birth and might represent a pertinent paradigm to approach the hemorrhage risk window observed in extreme preterms. Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways. Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways. Both approaches pointed towards extracellular matrix, cell adhesion and junction pathways, indicating delayed microvascular strengthening after P5. Furthermore, glutamate receptors, proteases and their inhibitors exhibited convergent evolutions towards excitatory aminoacid sensitivity and low proteolytic control likely accounting for vascular vulnerability in P5 mice. Thus, age vascular specificities must be considered in future therapeutic interventions in preterms. Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.