A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats

Koranda, Jessica L.; Ruskin, David N.; Masino, Susan A.; Blaise, J.H.

doi:10.1152/jn.00001.2011

Cited by 28 publications

(27 citation statements)

References 50 publications

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“…We also found a lack of effect of KD feeding on working memory in control mouse strains [48] and a lack of effect on baseline hippocampal electrophysiology in vitro in control strains (but an impact on chemically-induced epileptiform activity; [56]). We found normal in vivo baseline hippocampal field potential activity (but a lessening of induced seizures or tetanus-induced potentiation; [53,54,57]. Work from other laboratories is largely in agreement (for instance [76,77]).…”

Section: Discussionsupporting

confidence: 63%

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ruskin

Fortin

Bisnauth

et al. 2017

Physiology & Behavior

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The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5 weeks of age. Beginning at 8 weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females.

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Section: Discussionsupporting

confidence: 63%

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ruskin

Fortin

Bisnauth

et al. 2017

Physiology & Behavior

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“…In freely behavioural rats, a ketogenic diet-although not significantly altering baseline excitability-did reduce the magnitude of long-term potentiation plastic mechanisms in the hippocampal dentate gyrus [11,25]. Our results seem to be in perfect agreement with those provided by the animal models.…”

Section: Discussionsupporting

confidence: 85%

“…This avoids any influence on the initial facilitatory mechanism. Reduced potentiation/hyperresponsivity mechanisms in ketogenic diet-fed rats [11,25] is consistent with a general modulation of cortical excitability. This was confirmed by the observation that KD is a useful tool in controlling childhood seizures [27,28].…”

Section: Discussionsupporting

confidence: 61%

1. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study

Bracaglia¹,

Lorenzo²,

Lenola³

et al. 2016

Clinical Neurophysiology

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Background: Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. Methods: Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. Results: After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks. Conclusions: KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

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“…The lack of a standard protocol for a “diet in a dish” is evident in the diversity of experimental procedures, the prevalence of mixed results and the relative dearth of studies given the importance of delineating the key mechanisms underlying an enduring and successful treatment for a common and challenging neurological condition. In vivo recording clearly does not have this problem because it uses the whole body of experimental animals and diet-altered metabolism is maintained (Koranda et al, 2011; Masino et al, 2011). Several special strategies have been implemented for examining mechanisms of the ketogenic diet using hippocampal slice preparations; we focus on reviewing three of these approaches (Figures 1–3).…”

Section: Advantages Of the Hippocampal Slice Preparation In Studying mentioning

confidence: 99%

Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

Kawamura

Ruskin

Masino

2016

Front. Mol. Neurosci.

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The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

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A ketogenic diet reduces long-term potentiation in the dentate gyrus of freely behaving rats

Cited by 28 publications

References 50 publications

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse

1. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: A multimodal evoked potentials study

Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

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