The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study

Zhu, Yuankai; Tang, Xiangyu; Cheng, Zhaoting; Dong, Qingjian; Ruan, Ge

doi:10.1155/2022/3506213

Cited by 7 publications

(8 citation statements)

References 64 publications

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“…However, studies are available on the anti-inflammatory effect of the diet strictly in PD. Among other studies, a publication in 2022 demonstrated that the anti-inflammatory effect of the ketogenic diet in the disease is related to a modulation of the Akt/GSK-3β/CREB signalling pathway, mediated by the acetylation of metabotropic glutamate receptor 5 (mGluR5) promoter region histones in a rat Parkinson’s disease model [ 183 ]. This study confirmed mainly the neuroprotective effect of preventive ketosis compared to receiving KD as a therapeutic diet in the lipopolysaccharide (LPS)-induced rat PD model.…”

Section: The Role Of the Ketogenic Diet In The Therapy Of Parkinson’s...mentioning

confidence: 99%

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The Role of Ketogenic Diet in the Treatment of Neurological Diseases

2022

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Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.

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Section: The Role Of the Ketogenic Diet In The Therapy Of Parkinson’s...mentioning

confidence: 99%

“…Ketone bodies serve not only as an energy substrate but also as a signalling molecule. Finally, microglial cells can be modulated by various epigenetic mechanisms (DNA methylation and histone acetylation) and, thus, regulate neuroinflammation, resulting in neuroprotection [ 183 ].…”

Section: The Role Of the Ketogenic Diet In The Therapy Of Parkinson’s...mentioning

confidence: 99%

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

2022

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“…In the LPS-stimulated rat PD model, KD exerted an anti-inflammatory effect that was associated with the regulation of the Akt/GSK-3β/CREB signaling pathway facilitated by the histone acetylation of the mGluR5 promotor region [ 47 ]. Thus, targeting mGluR5 with epigenetic modification could be a promising approach to attenuate the microglia triggering in PD.…”

Section: Resultsmentioning

confidence: 99%

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

et al. 2023

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Background: The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its popularity has focused on the treatment of obesity and diabetes mellitus. KD also exerts anti-inflammatory and neuroprotective properties, which could be utilized for the therapy of neurodegenerative and psychiatric disorders. Purpose: This is a thorough, scoping review that aims to summarize and scrutinize the currently available basic research performed in in vitro and in vivo settings, as well as the clinical evidence of the potential beneficial effects of KD against neurodegenerative and psychiatric diseases. This review was conducted to systematically map the research performed in this area as well as identify gaps in knowledge. Methods: We thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar, to obtain the most recent in vitro and in vivo data from animal studies as well as clinical human surveys from the last twenty years, applying effective and characteristic keywords. Results: Basic research has revealed multiple molecular mechanisms through which KD can exert neuroprotective effects, such as neuroinflammation inhibition, decreased reactive oxygen species (ROS) production, decreased amyloid plaque deposition and microglial activation, protection in dopaminergic neurons, tau hyper-phosphorylation suppression, stimulating mitochondrial biogenesis, enhancing gut microbial diversity, restoration of histone acetylation, and neuron repair promotion. On the other hand, clinical evidence remains scarce. Most existing clinical studies are modest, frequently uncontrolled, and merely assess the short-term impacts of KD. Moreover, several clinical studies had large dropout rates and a considerable lack of compliance assessment, as well as an increased level of heterogeneity in the study design and methodology. Conclusions: KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.

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“…IL-6 is detectable in brain lesions (103) and in the CSF from people with MS (104) and plays critical roles in MS and EAE pathophysiology that include compromising blood-brain barrier integrity in combination with IL-17A (105), cooperating with transforming growth factor-b to drive the differentiation and expansion of auto-reactive TH17 cells (106)(107)(108)(109), and damaging myelin (102). Reduced circulating IL-6 by a KD has been reported (e.g., (110)(111)(112)(113)(114)(115)(116)) although studies in select populations (e.g., (117,118) and some mouse models have also reported that a KD may not change or may even increase levels of this cytokine (e.g., (119)). Reduced levels of IL-6 in the serum of KD-fed EAE mice are consistent with this dietary approach blunting CNS disease burden and maintaining motor and visual functions.…”

Section: Discussionmentioning

confidence: 99%

Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis

Zyla-Jackson

Walton

Plafker

et al. 2022

Preprint

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5-8% of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the CNS, these treatments are restricted to subsets of patients. To overcome these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by patients with multiple sclerosis. Here, we report that limiting dietary carbohydrates by feeding mice a well-formulated ketogenic diet (WFKD) enriched in medium chain triglycerides, alpha-linolenic acid, and fiber protects from EAE-induced optic neuritis and motor deficits. The WFKD increased circulating ketones but did not cause weight gain while preserving visual acuity and motor function in both female and male EAE mice. Immunohistochemistry of optic nerves revealed that the WFKD preserved oligodendrocytes and reduced infiltrating T cells and macrophages. The WFKD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with inflammation and EAE pathologies. In support of ongoing clinical trials using dietary strategies to treat MS patients, these findings support that a WFKD promotes a systemic anti-inflammatory milieu that mitigates autoimmune-induced demyelinating visual and motor deficits.

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The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson’s Disease Model: A Dual-Tracer PET Study

Cited by 7 publications

References 64 publications

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis

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