Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo.
OBJECTIVE
The ketogenic diet (KD) is an effective treatment for intractable epilepsy. However, little is known about its underlying mechanisms.


METHODS
In this study, in vivo extracellular field responses to angular bundle stimulation were recorded in the dentate gyrus of Sprague-Dawley rats fed one of three diets: ketogenic calorie-restricted (KCR), normal calorie-restricted (NCR), or normal ad libitum (NAL). Input/output curves and paired-pulse relations were used to assess network excitability. A maximal dentate activation (MDA) protocol was used to measure electrographic seizure threshold and duration.


RESULTS
Animals fed calorie-restricted (CR) diets exhibited greater paired-pulse inhibition, an elevated MDA threshold, and an absence of spreading depression-like events compared with ad libitum-fed controls. In the MDA model of epileptogenesis, the rate of increase in electrographic seizure duration after repeated stimuli was markedly reduced in KCR-fed animals compared with NCR- and NAL-fed controls.


CONCLUSIONS
These data suggest that CR, by itself, can be anticonvulsant, and treatment with a KCR diet may be both anticonvulsant and antiepileptogenic.
Bough
Kristopher J
KJ
Emory University School of Medicine, Department of Pharmacology, Rollins Research Center, Atlanta, GA 30322, USA. kbough@emory.edu
Schwartzkroin
Philip A
PA
Rho
Jong M
JM
D000818:Animals; D031204:Caloric Restriction; D018891:Dentate Gyrus / Q000378:metabolism / Q000502:physiology*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004594:Electrophysiology; D004827:Epilepsy / Q000178:diet therapy* / Q000378:metabolism / Q000517:prevention & control*; D005526:Food, Formulated; D006801:Humans; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism; D007662:Ketosis / Q000139:chemically induced* / Q000378:metabolism; D007696:Kindling, Neurologic / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007657:Ketone Bodies