Physiological and neurochemical differences between audiogenic and nonaudiogenic seizure mice

DBA mice are susceptible to audiogenic seizures in an age-dependent manner being maximally susceptible at 21 days. Anion transport (radioiodide uptake) was determined in tissues from DBA and AGS-resistant C57BL/6J mice at three ages. In thyroid, DBA mice had an enhanced ability to concentrate iodide at 21 days. Also, DBA mice at 21 days had increased iodide in the CSF and a lower ratio of cerebral cortex to CSF iodide suggesting that DBA mice have decreased transport of iodide into cerebral cortical cells from brain interstitial fluid. Activity of transport enzymes were also determined. DBA mice had higher CA activity in whole brain homogenates and in several subcellular fractions from brain at 21 days. Also, DBA mice at 21 days had a higher Na('+),K('+)-ATPase activity in myelin from cerebral cortex, and a lower HCO(,3)('-)-ATPase activity in mitochondria from brainstem. Most of these differences in enzymatic activity were not present at older ages. The effect of acute and chronic administration of acetazolamide (ACTZ), an inhibitor of CA, was also determined. ACTZ ED(,50)s against MES was significantly higher in DBA versus C57 mice at 26, 36 and 115 days. ACTZ ED(,50)s against AGSs in DBA mice were considerably lower than ACTZ ED(,50)s against MES in either strain suggesting that a particular fraction of CA is involved in the production of AGSs. These studies also demonstrated that DBA mice cannot develop tolerance to the effects of CA and that EST was significantly lower in DBA mice at various ages. The electrolyte content, extracellular space and DNA content of brain from DBA and C57 mice were also determined. Intracellular chloride and sodium contents were decreased, intracellular potassium content was increased, and extracellular space was increased in brain from DBA mice at 21 and 110 days. In addition, DNA content was lower in cerebellum of DBA mice at 110 days. These findings are further evidence of alterations in transport of anions and of changes in the cellular composition of brain from DBA mice. Such changes may contribute to AGS susceptibility by disruptig the balance that normally exists in the neuronal environment of the CNS.