A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study

Calderon, N.; Betancourt, Luis; Hernández, Luis; Rada, Pedro

doi:10.1016/j.neulet.2017.02.014

Cited by 70 publications

(41 citation statements)

References 43 publications

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“…Indeed, KD can induce an increase in glutamate decarboxylase expression in the striatum of rats ( Cheng et al, 2004 ) and an alteration of astrocytic GABA degradation via a modification of GABA transaminase activity ( Suzuki et al, 2009 ). Moreover, GABA content is increased by KBs in rat brain synaptosomes ( Erecinska et al, 1996 ), rat hippocampus ( Calderon et al, 2017 ), and in the brain of patients ( Wang et al, 2003 ). Some authors have reported the inhibition of glutamatergic, synaptic transmission ( Danial et al, 2013 ; Lutas and Yellen, 2013 ), which implies a blockade of vesicular glutamate transporters ( Juge et al, 2010 ).…”

Section: Protective Effects Of Kd On the Neuromuscular Systemmentioning

confidence: 99%

How Can a Ketogenic Diet Improve Motor Function?

Veyrat-Durebex

Reynier

Procaccio

et al. 2018

Front. Mol. Neurosci.

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A ketogenic diet (KD) is a normocaloric diet composed by high fat (80–90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction.

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Section: Protective Effects Of Kd On the Neuromuscular Systemmentioning

confidence: 99%

How Can a Ketogenic Diet Improve Motor Function?

Veyrat-Durebex

Reynier

Procaccio

et al. 2018

Front. Mol. Neurosci.

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“…Given this information, it probably comes as no surprise to learn that astrocyte dysfunction, astrogliosis, and the accompanying global loss of the physiological functions of astrocytes in the regulation of CNS homeostasis play a major role in the development and acceleration of most if not all neurodegenerative [185,186] and neuroprogressive disorders [187,188]. In addition, treating the causes and/or consequences of astrogliosis is a major therapeutic objective [61,63,166].…”

Section: Consequences Of Astrogliosismentioning

confidence: 99%

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

et al. 2020

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Nutritional ketosis, induced via either the classical ketogenic diet or the use of emulsified medium-chain triglycerides, is an established treatment for pharmaceutical resistant epilepsy in children and more recently in adults. In addition, the use of oral ketogenic compounds, fractionated coconut oil, very low carbohydrate intake, or ketone monoester supplementation has been reported to be potentially helpful in mild cognitive impairment, Parkinson’s disease, schizophrenia, bipolar disorder, and autistic spectrum disorder. In these and other neurodegenerative and neuroprogressive disorders, there are detrimental effects of oxidative stress, mitochondrial dysfunction, and neuroinflammation on neuronal function. However, they also adversely impact on neurone–glia interactions, disrupting the role of microglia and astrocytes in central nervous system (CNS) homeostasis. Astrocytes are the main site of CNS fatty acid oxidation; the resulting ketone bodies constitute an important source of oxidative fuel for neurones in an environment of glucose restriction. Importantly, the lactate shuttle between astrocytes and neurones is dependent on glycogenolysis and glycolysis, resulting from the fact that the astrocytic filopodia responsible for lactate release are too narrow to accommodate mitochondria. The entry into the CNS of ketone bodies and fatty acids, as a result of nutritional ketosis, has effects on the astrocytic glutamate–glutamine cycle, glutamate synthase activity, and on the function of vesicular glutamate transporters, EAAT, Na+, K+-ATPase, Kir4.1, aquaporin-4, Cx34 and KATP channels, as well as on astrogliosis. These mechanisms are detailed and it is suggested that they would tend to mitigate the changes seen in many neurodegenerative and neuroprogressive disorders. Hence, it is hypothesized that nutritional ketosis may have therapeutic applications in such disorders.

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“…KB are used as an alternative source of energy instead of brain glucose in individuals on KD. When the KB arrive in the brain, they are converted into acetyl-CoA and enter the cycle of tricarboxylic acid at the level of the brain mitochondria, by which adenosine triphosphate (ATP) is obtained [32]. It has been seen that the ketone bodies (KB) and polyunsaturated fatty acids (PUFAs), which can be enhanced under KD, may play main roles in producing anti-seizure effects [8].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…In turn, glutamine would be incorporated by neurons and converted into GABA, which would perform its inhibitory functions [36]. High levels of agmatine, a small inhibitory neurotransmitter with neuroprotective properties, have been found in the hippocampus in animal models treated with KD [32]. Monoamine neurotransmitters, including norepinephrine, dopamine, and serotonin, also have ongoing KD changes.…”

mentioning

confidence: 99%

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Diet in the Treatment of Epilepsy: What We Know So Far

Verrotti¹,

Iapadre²,

Francesco³

et al. 2020

Nutrients

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Epilepsy is a chronic and debilitating neurological disorder, with a worldwide prevalence of 0.5–1% and a lifetime incidence of 1–3%. An estimated 30% of epileptic patients continue to experience seizures throughout life, despite adequate drug therapy or surgery, with a major impact on society and global health. In recent decades, dietary regimens have been used effectively in the treatment of drug-resistant epilepsy, following the path of a non-pharmacological approach. The ketogenic diet and its variants (e.g., the modified Atkins diet) have an established role in contrasting epileptogenesis through the production of a series of cascading events induced by physiological ketosis. Other dietary regimens, such as caloric restriction and a gluten free diet, can also exert beneficial effects on neuroprotection and, therefore, on refractory epilepsy. The purpose of this review was to analyze the evidence from the literature about the possible efficacy of different dietary regimens on epilepsy, focusing on the underlying pathophysiological mechanisms, safety, and tolerability both in pediatric and adult population. We believe that a better knowledge of the cellular and molecular biochemical processes behind the anticonvulsant effects of alimentary therapies may lead to the development of personalized dietary intervention protocols.

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A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study

Cited by 70 publications

References 43 publications

How Can a Ketogenic Diet Improve Motor Function?

How Can a Ketogenic Diet Improve Motor Function?

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

Diet in the Treatment of Epilepsy: What We Know So Far

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