Paired-Pulse Inhibition and Maximal Dentate Activation Protocols Suggest Decreased Excitability in Ketogenic Diet-Fed Rats In Vivo
Abstract number :
3.144
Submission category :
Year :
2001
Submission ID :
2187
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
K.J. Bough, PhD, Neurological Surgery, University of Washington, Seattle, WA; A. Emmi, MD, PhD, Neurological Surgery, University of Washington, Seattle, WA; S.X. Rejniak, AB, Neurological Surgery, University of Washington, Seattle, WA; J.M. Rho, MD, Pedia
RATIONALE: Assessment of ketogenic diet (KD)-induced effects on synaptic excitability has proven difficult to accomplish in vitro, since standard culture bathing media contain glucose which would be expected to alter the cellular environment of tissue from KD-fed animals. The present study was designed to test in vivo the hypothesis that KD-fed animals exhibit less synaptic excitability than do control-fed animals.
METHODS: Beginning at postnatal day 37 (P37), male Sprague-Dawley rats were fed one of three diets: a calorie-restricted ketogenic diet (KCR), a calorie-restricted normal chow diet (NCR), or an ad libitum normal chow diet (NAL). At P65-75, animals were anesthetized with urethane, holes were drilled in the skull, and a stimulating electrode was directed toward the angular bundle while a saline-filled microelectrode was directed toward the dentate granule cell layer. A paired-pulse stimulation protocol was used to assess the degree of synaptic excitability in the dentate gyrus. A maximal dentate activation (MDA) protocol was also used, to assess diet effects on electrographic seizure duration.
RESULTS: At an interpulse interval (IPI) of 30 ms and a frequency of 0.1 Hz, animals fed either a KCR or NCR diet exhibited greater paired-pulse inhibition than did NAL fed-controls; paired-pulse responses at all other intervals tested (70, 150, 250, 500, and 750 ms) did not show marked differences. Stimulating at 1.0 Hz, we found no differences in paired-pulse inhibition at any IPI. While NCR- and NAL-fed animals showed an increase in electrographic seizure duration in response to repeated MDA stimuli, animals fed a KCR diet showed no such enhancement.
CONCLUSIONS: Both KCR- and NCR-fed animals exhibit more fast feedback inhibition than NAL-fed control rats, suggesting that GABA-mediated responses are augmented by calorie-restriction. Further, KCR-fed animals appear resistant to changes (i.e., increases) in MDA duration that is typical of the control rats when stimulated repeatedly. This result suggests that KD treatment may have antiepileptic properties.
Support: This project was sponsored by the American Epilepsy Society (KJB) and the UW Pediatric Epilepsy Research Center (PERC).