The pentylenetetrazole-kindling model of epilepsy in SAMP8 mice: glial-neuronal metabolic interactions.
Recently, a new experimental model of epilepsy was introduced by the authors [Neurochem. Int. 40 (2002) 413]. This model combines pentylenetetrazole (PTZ)-kindling in senescence-accelerated mice P8 (SAMP8), a genetic model of aging. Since imbalance of glutamate and GABA is a major cause of seizures, the study of glial-neuronal interactions is of primary importance. Nuclear magnetic resonance spectroscopy (NMRS) is an excellent tool for metabolic studies. Thus, we examined whether NMRS when combined with administration of [1-13C]glucose and [1,2-13C]acetate might give valuable insights into neurotransmitter metabolism in this new model of epilepsy and aging. The 2- and 8-month-old SAMP8 were kindled with PTZ alone, received PTZ and phenobarbital (PB), or served as controls. In older animals, PTZ-kindling decreased labeling in glutamate C-4 from [1-13C]glucose, whereas, in the younger mice, labeling in glutamine C-4 was decreased both from [1-13C]glucose and [1,2-13C]acetate. It could be concluded that PTZ-kindling affected astrocytes in younger and glutamatergic neurons in older animals. In the presence of PTZ, phenobarbital decreased labeling of most metabolites in all cell types, except GABAergic neurons, from both labeled precursors in the younger animals. However, in older animals only GABAergic neurons were affected by phenobarbital as indicated by an increase in GABA labeling.
Kondziella
Daniel
D
Department of Neuroscience and Locomotion, Norwegian University of Science and Technology, Trondheim, Norway.
Hammer
Janniche
J
Sletvold
Olav
O
Sonnewald
Ursula
U
D019342:Acetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003292:Convulsants; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007696:Kindling, Neurologic; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology
D000927:Anticonvulsants; D003292:Convulsants; D005947:Glucose; D019342:Acetic Acid; D010433:Pentylenetetrazole; D010634:Phenobarbital