» Articles » PMID: 34381166

Ketogenesis Controls Mitochondrial Gene Expression and Rescues Mitochondrial Bioenergetics After Cervical Spinal Cord Injury in Rats

Overview
Journal Sci Rep
Specialty Science
Date 2021 Aug 12
PMID 34381166
Citations 13
Authors
Affiliations
Soon will be listed here.
Abstract

A better understanding of the secondary injury mechanisms that occur after traumatic spinal cord injury (SCI) is essential for the development of novel neuroprotective strategies linked to the restoration of metabolic deficits. We and others have shown that Ketogenic diet (KD), a high fat, moderate in proteins and low in carbohydrates is neuroprotective and improves behavioural outcomes in rats with acute SCI. Ketones are alternative fuels for mitochondrial ATP generation, and can modulate signaling pathways via targeting specific receptors. Here, we demonstrate that ad libitum administration of KD for 7 days after SCI rescued mitochondrial respiratory capacity, increased parameters of mitochondrial biogenesis, affected the regulation of mitochondrial-related genes, and activated the NRF2-dependent antioxidant pathway. This study demonstrates that KD improves post-SCI metabolism by rescuing mitochondrial function and supports the potential of KD for treatment of acute SCI in humans.

Citing Articles

Targeting mitochondrial function as a potential therapeutic approach for allergic asthma.

Chen D, Wu W, Li J, Huang X, Chen S, Zheng T Inflamm Res. 2025; 74(1):1.

PMID: 39762562 DOI: 10.1007/s00011-024-01972-8.


The impact of mild episodic ketosis on microglia and hippocampal long-term depression in 5xFAD mice.

Di Lucente J, Ramsey J, Jin L, Maezawa I FASEB Bioadv. 2024; 6(12):581-596.

PMID: 39650227 PMC: 11618890. DOI: 10.1096/fba.2024-00123.


Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in Rats: A Time-Course.

Seira O, Park H, Liu J, Poovathukaran M, Clarke K, Boushel R Cells. 2024; 13(21.

PMID: 39513853 PMC: 11545339. DOI: 10.3390/cells13211746.


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

Gureev A, Sadovnikova I, Chernyshova E, Tsvetkova A, Babenkova P, Nesterova V Int J Mol Sci. 2024; 25(11).

PMID: 38891898 PMC: 11172083. DOI: 10.3390/ijms25115710.


Mitochondrial dysfunction: mechanisms and advances in therapy.

Zong Y, Li H, Liao P, Chen L, Pan Y, Zheng Y Signal Transduct Target Ther. 2024; 9(1):124.

PMID: 38744846 PMC: 11094169. DOI: 10.1038/s41392-024-01839-8.


References
1.
Tang H, Lu J, Zheng X, Yang Y, Reagan J . The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. Biochem Biophys Res Commun. 2008; 375(4):562-5. DOI: 10.1016/j.bbrc.2008.08.041. View

2.
Qian J, Zhu W, Lu M, Ni B, Yang J . D-β-hydroxybutyrate promotes functional recovery and relieves pain hypersensitivity in mice with spinal cord injury. Br J Pharmacol. 2017; 174(13):1961-1971. PMC: 5466532. DOI: 10.1111/bph.13788. View

3.
Nguyen T, Huang H, Pickett C . Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem. 2000; 275(20):15466-73. DOI: 10.1074/jbc.M000361200. View

4.
Cullingford T, Eagles D, Sato H . The ketogenic diet upregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain. Epilepsy Res. 2002; 49(2):99-107. DOI: 10.1016/s0920-1211(02)00011-6. View

5.
Noh H, Lee H, Kim D, Kang S, Cho G, Rho J . A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet. Brain Res Mol Brain Res. 2004; 129(1-2):80-7. DOI: 10.1016/j.molbrainres.2004.06.020. View