Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats

Vizuete, Adriana Fernanda Kuckartz; Souza, Daniela Fraga de; Guerra, Maria Cristina; Batassini, Cristiane; Dutra, Márcio Ferreira; Bernardi, Caren Luciane; Costa, Ana Paula; Gonçalves, Carlos‐Alberto

doi:10.1016/j.lfs.2013.03.004

Cited by 24 publications

(19 citation statements)

References 60 publications

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“…Although, not statistically different, our findings are indicative of lower BDNF levels in both KD and KS control groups (7 and 8% lower, respectively). One other study described that feeding Wistar rats a KD for 8 weeks reduced BDNF levels in the striatum, but not the hippocampus (Vizuete et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

Brownlow

Jung

Moore

et al. 2017

Front. Mol. Neurosci.

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Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group. Our results highlight the complex relationship between peripheral metabolism, behavioral performance and biochemical changes in the hippocampus. Endogenous ketosis improved behavioral and metabolic parameters associated with energy metabolism and cognition while ketone supplementation replicated the biochemical effects within the hippocampus but only showed modest effects on behavioral improvements.

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Section: Discussionmentioning

confidence: 99%

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

Brownlow

Jung

Moore

et al. 2017

Front. Mol. Neurosci.

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“…A KD, but not a high fat or a low fat diet, led to a circadian shift in the expression of brain and liver BDNF, suggesting that a KD might impact (i) circadian activities, and (ii) the expression of BDNF [37]. However, the significance of neurotrophic factors as possible mediators of KD therapy are not yet clear, because in healthy rats a KD reduced BDNF levels in striatum, but not hippocampus, whereas the astrocyte neurotrophic cytokine S100β was not affected in the brain [38]. …”

Section: Neurotrophic Factorsmentioning

confidence: 99%

New insights into the mechanisms of the ketogenic diet

Boison

2017

Current Opinion in Neurology

209

150

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Purpose of review High-fat, low-carbohydrate ketogenic diets (KDs) have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of KDs has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of KD therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by KD therapies. Recent findings KDs act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium chain triclycerides, contributes to seizure control through direct AMPA receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. KD therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Summary KD therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

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“…Similarly, an eight-week KD provided to mice, as well as an omega-3 enriched KD; both led to approximately a 1.0ng/mL reduction in CSF S100β compared with controls and no change in S100β concentration in the hippocampus and striatum (137). Both studies (134,137) used experimental diets consisting of high amounts of lard, which is rich in SFA. However, a study analysing the hippocampal slices of rats fed a ketogenic diet found no significant difference in S100β after one or six weeks when compared with controls (138).…”

Section: S100β and Dietary Fatmentioning

confidence: 99%

“…Several reviews have discussed the potential application of the KD and KB in the treatment and prevention of neurodegenerative conditions including AD, through the management of dysfunctional insulin signalling and glucose metabolism (140,(188)(189)(190)(191). The reduced S100β levels observed in mice consuming a KD (134,137) is partly attributed to the production of BHB that can cross the BBB and provide energy to the brain as a safe alternative in the presence of impaired glucose metabolism (192). In addition, a KD in mice has also been shown to lower Aβ levels (193).…”

Section: Ketogenic Dietmentioning

confidence: 99%

Evaluation of dietary and lifestyle changes as modifiers of S100β levels in Alzheimer’s disease

D’Cunha

McKune

Panagiotakos

et al. 2017

Nutritional Neuroscience

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There is a significant body of research undertaken in order to elucidate the mechanisms underlying the pathology of Alzheimer's disease (AD), as well as to discover early detection biomarkers and potential therapeutic strategies. One such proposed biomarker is the calcium binding protein S100β, which, depending on its local concentration, is known to exhibit both neurotrophic and neuroinflammatory properties in the central nervous system. At present, relatively little is known regarding the effect of chronic S100β disruption in AD. Dietary intake has been identified as a modifiable risk factor for AD. Preliminary in vitro and animal studies have demonstrated an association between S100β expression and dietary intake which links to AD pathophysiology. This review describes the association of S100β to fatty acids, ketone bodies, insulin, and botanicals as well as the potential impact of physical activity as a lifestyle factor. We also discuss the prospective implications of these findings, including support of the use of a Mediterranean dietary pattern and/or the ketogenic diet as an approach to modify AD risk.

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Brain changes in BDNF and S100B induced by ketogenic diets in Wistar rats

Abstract: These findings reinforce the importance of this diet as an inductor of alterations in the brain, and such changes might contribute to the understanding of the effects (and side effects) of KD in brain disorders.

Cited by 24 publications

References 60 publications

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

New insights into the mechanisms of the ketogenic diet

Evaluation of dietary and lifestyle changes as modifiers of S100β levels in Alzheimer’s disease

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