Dataset Information

A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice.

ABSTRACT: Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer's disease and major depressive disorder. However, their effects on cognitive function in healthy individuals is less established. Here, we explored the mitochondrial and performative outcomes of a novel eight-week ketone-supplemented ketogenic (KETO) diet in healthy adult male and female mice. In a novel object recognition test, KETO mice spent more time with the novel, compared to familiar, object, indicating an improvement in recognition memory. High-resolution respirometry on permeabilized hippocampal tissue returned significant reductions in mitochondrial O₂ consumption. No changes in ATP production were observed, yielding a significantly higher ATP:O₂ ratio, a measure of mitochondrial efficiency. Together, these findings demonstrate the KETO diet improves hippocampal mitochondrial efficiency. They add to a growing body of evidence that suggests ketones and ketogenic diets are neuroprotective and metabolically and cognitively relevant, even in healthy adults. They also suggest that ketogenic lifestyle changes may be effective strategies for protecting against cognitive decline associated with aging and disease.

SUBMITTER: Saito ER

PROVIDER: S-EPMC9693360 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice.

Saito Erin R ER Warren Cali E CE Hanegan Cameron M CM Larsen John G JG du Randt Johannes D JD Cannon Mio M Saito Jeremy Y JY Campbell Rachel J RJ Kemberling Colin M CM Miller Gavin S GS Edwards Jeffrey G JG Bikman Benjamin T BT

Metabolites 20221025 11

Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer's disease and major depressive disorder. However, their effects on cognitive function in healthy individuals is less established. Here, we explored the mitochondrial and performative outcomes of a novel eight-week ketone-suppleme ...[more]

PMID: 36355101

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Project description:Obesity-related metabolic dysregulation causes mild cognitive impairment and increased risk for dementia. We used an LDLR-deficient C57BL/6J mouse model (LDLRKO) to investigate whether adropin, a neuropeptide linked to neurodegenerative diseases, improves cognitive function in situations of metabolic dysregulation. Adropin transgenic mice (AdrTG) were crossed with LDLRKO; male and female progeny were fed a high fat diet for 3-months. Male chow-fed wild type (WT) mice were used as controls. Diet-induced obesity and LDLR-deficiency caused severe dyslipidemia, irrespective of sex. The AdrTG prevented reduced adropin protein levels in LDLRKO cortex. In males, metabolic dysregulation and AdrTG genotype significantly and bi-directionally affected performance in the novel object recognition (NOR) test, a declarative hippocampal memory task (discrimination index mean ± SE for WT, 0.02 ± 0.088; LDLRKO, -0.115 ± 0.077; AdrTG;LDLRKO, 0.265 ± 0.078; genotype effect, p = 0.009; LDLRKO vs. AdrTG;LDLRKO, P < 0.05). A 2-way ANOVA (fixed variables: sex, AdrTG genotype) indicated a highly significant effect of AdrTG (P = 0.003). The impact of the diet-genotype interaction on the male mouse brain was investigated using RNA-seq. Gene-ontology analysis of transcripts showing fold-changes of>1.3 or <-1.3 (P < 0.05) indicated metabolic dysregulation affected gene networks involved in intercellular/neuronal signaling, immune processes, angiogenesis, and extracellular matrix organization. The AdrTG selectively attenuated the impact of metabolic dysregulation on intercellular/neuronal signaling pathways. Intercellular/neuronal signaling pathways were also the predominant processes overrepresented when directly comparing AdrTG;LDLRKO with LDRKO. In summary, adropin overexpression improves cognitive function in severe metabolic dysregulation through pathways related to cell-cell communication and neuronal processes, and independently of preventing inflammatory responses.

Dataset Information

A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice.

Publications

A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice.

Similar Datasets

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