The Ketogenic Diet but not Hydroxycitric Acid Keeps Brain Mitochondria Quality Control and mtDNA Integrity Under Focal Stroke

Gureev, Artem P.; Silachev, Denis N.; Sadovnikova, Irina S.; Krutskikh, Ekaterina P.; Chernyshova, Ekaterina V; Volodina, Daria E; Samoylova, Nataliya A.; Potanina, Daria V.; Burakova, Inna; Smirnova, Yuliya; Popov, Vasily N.; Plotnikov, Egor Y.

doi:10.1007/s12035-023-03325-8

Cited by 4 publications

(3 citation statements)

References 73 publications

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“…On the contrary, in injury, especially spinal cord injury, mTOR levels increased under a ketogenic diet, as did levels of Nrf2-dependent proteins [ 59 ]. Previously, we showed that the expression of Nfe2l2 and a number of Nrf2-related genes increased in mice fed a ketogenic diet after stroke [ 60 ]. Similar results were obtained in the current work.…”

Section: Discussionmentioning

confidence: 99%

“…The maintaining of mitochondrial stability is also critical for adequate brain function, especially for cognitive processes [ 69 ]. We have previously shown that mtDNA has accumulated a significant amount of damage in the penumbra zone 3 days after photothrombosis [ 60 ]. The amount of mtDNA damage was increased in all mtDNA fragments in the PT + water group 3 days after the surgery.…”

Section: Discussionmentioning

confidence: 99%

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Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice

Gureev,

Sadovnikova,

Chernyshova

et al. 2024

IJMS

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The consequences of stroke include cognitive deficits and sensorimotor disturbances, which are largely related to mitochondrial impairments in the brain. In this work, we have shown that the mimetic of the ketogenic diet beta-hydroxybutyrate (βHB) can improve neurological brain function in stroke. At 3 weeks after photothrombotic stroke, mice receiving βHB with drinking water before and after surgery recovered faster in terms of sensorimotor functions assessed by the string test and static rods and cognitive functions assessed by the Morris water maze. At the same time, the βHB-treated mice had lower expression of some markers of astrocyte activation and inflammation (Gfap, Il-1b, Tnf). We hypothesize that long-term administration of βHB promotes the activation of the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway, which leads to increased expression of antioxidant genes targeting mitochondria and genes involved in signaling pathways necessary for the maintenance of synaptic plasticity. βHB partially maintained mitochondrial DNA (mtDNA) integrity during the first days after photothrombosis. However, in the following three weeks, the number of mtDNA damages increased in all experimental groups, which coincided with a decrease in Ogg1 expression, which plays an important role in mtDNA repair. Thus, we can assume that βHB is not only an important metabolite that provides additional energy to brain tissue during recovery from stroke under conditions of mitochondrial damage but also an important signaling molecule that supports neuronal plasticity and reduces neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice

Gureev,

Sadovnikova,

Chernyshova

et al. 2024

IJMS

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“…KBs and KD have demonstrated the ability to enhance mitochondrial function in cerebral ischemia and neurodegenerative diseases [ 26 , 69 , 98 , 99 , 100 , 101 ]. The molecular mechanism underlying the beneficial effects of KBs and KD involves increased NADH oxidation via KB catabolism [ 39 , 82 ].…”

Section: Molecular Mechanisms Of the Neuroprotective Effects Of Kbs A...mentioning

confidence: 99%

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

Jang,

Kim,

Lee

et al. 2023

IJMS

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Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.

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Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway

Cao

Wang

Xie

et al. 2023

European Journal of Pharmacology

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The Ketogenic Diet but not Hydroxycitric Acid Keeps Brain Mitochondria Quality Control and mtDNA Integrity Under Focal Stroke

Cited by 4 publications

References 73 publications

Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice

Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

Ketogenic diet and β-Hydroxybutyrate alleviate ischemic brain injury in mice via an IRAKM-dependent pathway

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