Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

TY - JOUR

T1 - Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

AU - Hansen, Suzanne L

AU - Nielsen, Ane H

AU - Knudsen, Katrine E

AU - Artmann, Andreas

AU - Kristiansen, Uffe

AU - Hansen, Steen Honore'

AU - Hansen, Harald S

AU - Petersen, Gitte

N1 - Keywords: Animals; Convulsants; Disease Models, Animal; Down-Regulation; Endocannabinoids; Epilepsy; Ethanolamines; Hippocampus; Ketogenic Diet; Kindling, Neurologic; Male; Mice; Oleic Acids; Pentylenetetrazole; Receptor, Cannabinoid, CB1

PY - 2009

Y1 - 2009

N2 - The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure activity may mediate neuroprotection as may several N-acylethanolamines. It is unknown how the KD interfere with the endocannabinoid system. We investigated the antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in young mice and measured the hippocampal levels of CB(1)-R by Western blot and of endocannabinoids and N-acylethanolamines by mass spectrometry. The KD significantly decreased incidence and severity of seizures, and significantly increased the latency to clonic convulsions. There were no changes in levels of endocannabinoids or CB(1)-R expression by either seizure activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does not support a role of endocannabinoids in this model. The significance of the decreased hippocampal level of oleoylethanolamide awaits further studies.

AB - The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure activity may mediate neuroprotection as may several N-acylethanolamines. It is unknown how the KD interfere with the endocannabinoid system. We investigated the antiepileptogenic potential of the KD in the pentylenetetrazole kindling model in young mice and measured the hippocampal levels of CB(1)-R by Western blot and of endocannabinoids and N-acylethanolamines by mass spectrometry. The KD significantly decreased incidence and severity of seizures, and significantly increased the latency to clonic convulsions. There were no changes in levels of endocannabinoids or CB(1)-R expression by either seizure activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does not support a role of endocannabinoids in this model. The significance of the decreased hippocampal level of oleoylethanolamide awaits further studies.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.neuint.2008.10.012

DO - 10.1016/j.neuint.2008.10.012

M3 - Journal article

C2 - 19100800

SN - 0197-0186

VL - 54

SP - 199

EP - 204

JO - Neurochemistry International

JF - Neurochemistry International

IS - 3-4

ER -