Table 1.
Mouse Model | A1R Expression | Predicted change in seizure frequency | Observed change in seizure frequency | Glucose-induced change in seizure frequency |
---|---|---|---|---|
Wild-type: (C57/BL6) | unaltered | n/a (no seizures) | n/a | no change |
Transgenic: Adk-tg | unaltered | robust Suppression | 88% decrease (p<0.001) | reversed to 85% of baseline (p<0.001) |
Transgenic: A1R+/− | 50% normal | partial suppression | 53% decrease (p<0.001) | reversed to 89% of baseline (p<0.001) |
Transgenic: A1R−/− | no receptors | no Suppression | 4% decrease (n.s.) | no change (n.s.) |
Legend: Predicted and observed effects of a ketogenic diet in a complement of wild type and transgenic mice. All transgenic mice demonstrated adenosine-based recurrent electrographic seizures. Based on the level of A1R expression in each mouse strain we predicted the correlated effects of a ketogenic diet in reducing seizure frequency. The A1R receptor gene was not manipulated in the Adk-tg mice; thus, we predicted seizures would be reduced by a ketogenic diet. We observed a significant (88%) reduction in seizure frequency. Functional A1Rs are expressed partially (50%) in the A1R+/− mice, and thus we predicted partial seizure reduction. We observed that seizures decreased significantly but to a lesser extent than in the Adk-tg mice (53%). Finally, A1R−/− mice have a complete loss of functional A1Rs, we predicted no effects of the ketogenic diet on spontaneous seizures, and we observed no significant change (4%) in seizure frequency. The ketogenic diet-induced decrease in seizure frequency was reversed significantly by glucose injection in Adk-tg and A1R+/− mice, and electrographic activity was unaffected in wild-type and A1R−/− mice (adapted from Masino et al., 2011)