Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice.

Autor: Mahajan VR; Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA.; Laboratory for Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Nadel JA; Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., King MT; Laboratory for Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Pawlosky RJ; Laboratory for Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Davis MI; Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Veech RL; Laboratory for Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Lovinger DM; Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA., Salinas AG; Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA.; Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center - Shreveport, Shreveport, Louisiana, USA.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2024 Dec; Vol. 60 (11), pp. 6875-6890. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1111/ejn.16601
Abstrakt: Parkinson's disease (PD) is a progressive, neurodegenerative disease characterized by motor dysfunction and dopamine deficits. The MitoPark (MP) mouse model of PD recapitulates several facets of Parkinson's disease, including gradual development of motor deficits, which enables the study of potential therapeutic interventions. One therapeutic strategy involves decreasing the mitochondrial metabolic load by inducing ketosis and providing an alternative energy source for neurons, leading to decreased neuronal oxidative stress. Thus, we hypothesized that administration of a ketone ester-enriched diet (KEED) would improve motor and dopamine release deficits in MP mice. Motor function (rotarod and open field tests), dopamine release (fast-scan cyclic voltammetry), tissue dopamine levels (gas chromatography-mass spectrometry) and dopamine neurons and axons (immunofluorescence) were assessed in MP, and control mice fed either the standard or a KEED. When started on the ketone diet before motor dysfunction onset, MP mice had improved motor function relative to standard diet (SD) MP mice. While the KEED did not preserve dopamine neurons or striatal dopamine axons, dopamine release in ketone diet MP mice was greater than SD MP mice but less than control mice. In a follow-up experiment, we began the ketone diet after motor dysfunction onset and observed a modest preservation of motor function in ketone diet MP mice relative to SD MP mice. The improvement in motor dysfunction indicates that a KEED or ketone supplement may have a beneficial effect on delaying motor deficit progression in Parkinson's disease.
(© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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