Some Age‐Dependent Biochemical Changes in Mice Susceptible to Seizures

Abstract

Summary Mice susceptible to audiogenic seizures (DBA strain) and mice not susceptible (C57 strain) were tested by elevating the body temperature. At 30 days of age 64% of the DBA mice developed convulsions and one‐quarter died, whereas only 1 of 20 of the C57 mice had a convulsion although one‐fifth died. At 20 days 15% of DBA mice had a convulsion, at 40 days none did. Mice of the DBA strain thus seem to be a valid animal model of febrile convulsions in humans. At the age of peak susceptibility to convulsions, but not before or after, the brains of DBA mice had marked diminution in (Na, K)‐activated ATPase, diminished concentration of K+, diminished K+‐stimulated release of GABA, and diminished oxygen uptake. The neurochemical alterations point to a genetically determined age‐dependent enzyme deficit in the brain with resultant ionic and metabolic changes that might contribute to seizure susceptibility. RÉsumé On a testé des souris susceptibles (souche DBA) ou non (souche C57) de faire des crises audiogènes en élévant la température corporelle. A l'âge de 30 jours, 64% des souris de la souche DBA présentait des convulsions et 1/4 mourrait, tandis que seulement une souris sur 20 de la souche C57 avait des crises bien qu'un cinquième mourrait. A 20 jours d'âge, 15% des souris susceptibles avaient une crise, et à 40 jours aucune n'en présentait. Les souris de la souche DBA semblent done être un modèle animal valable pour l'étude des crises fébriles convulsives chez lliomme. A l'âge où la susceptibilityéà faire des convulsions est à son maximum, mais ni avant ni après, les cerveaux des souris de la souche DBA présentent une importante diminution en ATPase (Na, K)‐activée, une diminution du GABA libére par K+, et une diminution de la consommation en O2. Les modifications biochimiques pourraient mettre en évidence le déficit d'une enzyme cérébral génétiquement déterminée et dépendant de l'lâge, avec pour conséquences de modifications ioniques et métaboliques pouvant contribuer à la susceptibilityé aux crises. RESUMEN Mediante la elevación de la temperatura corporal se han estuidiado ratones susceptibles de tener ataques audiogenicos (raza DBA) y tambien ratones no susceptibles (raza C57). A los 30 dfas de edad un 64% de los ratones susceptibles (DBA) desarrollaron convulsiones y un 25% murieron, mientras que solamente 1 de los 20 ratones no susceptibles (C57) tuvieron convulsiones, aunque un 20% murieron. A los 20 días de edad, 15% de los ratones DBA tuvieron una convulsión y a los 40 días ninguno tuvo ataques. Así pues el ratón DBA parece ser un modelo animal válido para el estudio de las convulsiones febriles en humanos. A la edad de máxima susceptibilidad para convulsiones, y no antes o despues, los cerebros de los ratones DBA mostraron: gran reduccion de la (Na, K)‐activada ATPasa; disminución de la concentración de K+; descenso de la liberación de GABA, estimulada por el K+ y reduccion de la utilización de O2. Estas alteraciones neuroquimicas sugieren un defecto enzimático cerebral, genéticamente determ...

Kindling Susceptibility and Genetic Seizure Predisposition in Inbred Mice

“…Investigators comparing induction of two different kindling models within the same animal have usually noted that one type of seizure kindling increases vulnerability to another type of kindling (Cain, 1980(Cain, , 1981(Cain, , 1983Holmes and Weber, 1983), although occasional exceptions are noted (Okada et al, 1985; Thompson et al, 1988). Genetic models have almost unanimously demonstrated an increased vulnerability to other types of seizure inducement (Hamburgh and Vicari, 1960;Hertz et al, 1974;Deckard et al, 1976;Wada et al, 1976;Zhao et al, 1985;Savage et al, 1986;Sugaya et al, 1986). A single contradictory study comparing susceptibility to audiogenic seizures and vulnerability to hyperthermia-induced seizures in mice showed no cross-strain correlation between them, suggesting that separate genetic factors contribute to development of each of these features (Maxson, 1980).…”

Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs

“…However, in brain slices of DBA/2 mice at 30 days of age, the K + -stimulated release of GABA is considerably lower than that of C57 mice [35]. Furthermore, the number of GABA receptor binding sites is reduced in the brain of DBA/2 mice, while the affinities of these sites are higher than that in control mice of comparable age [59].…”

“…Microsomal Na + /K + ATPase activity in DBA/2 mice was reported to be depressed (vs C57) with a resulting decrease in intracellular K + concentration at the peak age of seizure susceptibility [35]; however, subsequent studies have failed to confirm this result [36]. The main neurotransmitter systems (i.e., GABA, excitatory amino acids, catecholamine, and serotonin) in the brain of DBA/2 mice have been the object of many studies.…”

Ontogeny of brain catecholamine turnover and susceptibility to audiogenic seizures in DBA/2J mice

“…Moreover, other age-related biochemical changes have also been demonstrated. For example, Hertz, Schousboe, Formby, and Lennox-Buchthal (1974) reported that at the age of peak AGS susceptibility DBA/2J mice had marked diminution in sodium-potassium-activated adenosine triphosphatase, diminished potassium, diminished potassium-stimulated release of gamma amino butyric acid, and diminished oxygen uptake.…”