Abstract:DBA/2J (DBA) mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner. Anion transport as measured by radioiodide uptake was determined in thyroid gland, salivary gland, skeletal muscle, cerebral cortex, cerebellum, brainstem, and CSF from these mice at various ages. Anion transport was also determined in C57BL/6J(C57) mice, an AS-resistant strain. In thyroid, DBA mice had an enhanced ability to concentrate iodide at 21 days of age when they have maximal AS susceptibility, as compared with … Show more
“…Since the role of CA in salivary gland tissue is uncertain, a decrease in activity of this enzyme here is of uncertain consequence. However, this finding does give additional support for an inverse relation between CA activity and 1251 transport, since 1251 transport is increased in salivary gland tissue from DBA mice at 21 days of age (Engstrom et al, 1984).…”
Section: Discussionmentioning
confidence: 82%
“…This relation is also present in DBA mice at 21 days. Thus, 1251 uptake studies in 21-day-old DBA mice demonstrated a decrease in iodide transport in cerebral cortex (Engstrom et al, 1984), and the present investigation demonstrated an increase in CA activity in cerebral cortex homogenates from DBA mice at this age. This finding may be explained if bicarbonate and iodide compete for the same transport system.…”
Section: Discussionmentioning
confidence: 85%
“…have also been investigated because a proper electrolyte balance in the neuronal microenvironment is essential for normal neuronal function. These investigations have shown that there is an alteration in anion transport of the brain of DBA mice (Engstrom et al, 1984; see review by Seyfried, 1982), suggesting that AS susceptibility may, at least in part, result from an electrolyte imbalance in the brain.…”
DBA/2J mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner, susceptibility being maximal at 21 days of age and declining thereafter. DBA, as compared with AS-resistant C57BL/6J (C57) mice, had higher carbonic anhydrase (CA) activity in cerebral cortex, brainstem, and cerebellum homogenates at 21 days of age. CA activity was also increased in cytosolic (82%), microsomal (167%), and myelin (68%) subcellular fractions from cerebral cortex, and in cytosolic (51%) and mitochondrial (102%) fractions from brainstem of DBA mice at 21 days of age. In addition, DBA mice had a higher Na+, K+-ATPase activity in myelin from cerebral cortex, and a lower HCO3--ATPase activity in mitochondria from brainstem. The differences in CA activity in the cerebral cortex and in HCO3--ATPase were not present at 110 days of age, when DBA mice are no longer susceptible to ASs. Because CA and HCO3--ATPase are involved in maintaining a proper ionic environment for neuronal function, these data suggest that alterations in activity of these enzymes are related to the age-dependent changes in AS susceptibility in DBA mice.
“…Since the role of CA in salivary gland tissue is uncertain, a decrease in activity of this enzyme here is of uncertain consequence. However, this finding does give additional support for an inverse relation between CA activity and 1251 transport, since 1251 transport is increased in salivary gland tissue from DBA mice at 21 days of age (Engstrom et al, 1984).…”
Section: Discussionmentioning
confidence: 82%
“…This relation is also present in DBA mice at 21 days. Thus, 1251 uptake studies in 21-day-old DBA mice demonstrated a decrease in iodide transport in cerebral cortex (Engstrom et al, 1984), and the present investigation demonstrated an increase in CA activity in cerebral cortex homogenates from DBA mice at this age. This finding may be explained if bicarbonate and iodide compete for the same transport system.…”
Section: Discussionmentioning
confidence: 85%
“…have also been investigated because a proper electrolyte balance in the neuronal microenvironment is essential for normal neuronal function. These investigations have shown that there is an alteration in anion transport of the brain of DBA mice (Engstrom et al, 1984; see review by Seyfried, 1982), suggesting that AS susceptibility may, at least in part, result from an electrolyte imbalance in the brain.…”
DBA/2J mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner, susceptibility being maximal at 21 days of age and declining thereafter. DBA, as compared with AS-resistant C57BL/6J (C57) mice, had higher carbonic anhydrase (CA) activity in cerebral cortex, brainstem, and cerebellum homogenates at 21 days of age. CA activity was also increased in cytosolic (82%), microsomal (167%), and myelin (68%) subcellular fractions from cerebral cortex, and in cytosolic (51%) and mitochondrial (102%) fractions from brainstem of DBA mice at 21 days of age. In addition, DBA mice had a higher Na+, K+-ATPase activity in myelin from cerebral cortex, and a lower HCO3--ATPase activity in mitochondria from brainstem. The differences in CA activity in the cerebral cortex and in HCO3--ATPase were not present at 110 days of age, when DBA mice are no longer susceptible to ASs. Because CA and HCO3--ATPase are involved in maintaining a proper ionic environment for neuronal function, these data suggest that alterations in activity of these enzymes are related to the age-dependent changes in AS susceptibility in DBA mice.
“…Additional studies have shown that there is a decrease in anion transport in cerebral cortical cells of DBA mice at the age of maximal susceptibility to AGSs (Engstrom et al, 1984). Also, it has been shown that there is a decrease in density and an increase in atfinity of GABA binding sites in brain from DBA mice when they are susceptible to AGSs (see review by Seyfried, 1982).…”
Section: Discussion Mest Glycine and Excitatory Amino Acidsmentioning
Convulsive dose 50s (CD50s) for various convulsive drugs and minimal and maximal electroshock seizure thresholds were determined in DBA and C57 mice. DBA mice had lower maximal electroshock seizure thresholds (MESTs, 15%) and CD50s for homocysteine thiolactone (HTL, 23%) and bicuculline (69%), and a higher CD50 for pentylenetetrazol (PTZ) at 3 weeks of age, the age of maximal audiogenic seizure (AGS) susceptibility. At 8 weeks, when DBA mice are not susceptible to AGSs, significant differences were a lower minimal electroshock seizure threshold (mEST, 37%) and maximal EST (MEST) (19%), lower CD50s for N-methyl-D-aspartate (NMDA) (39%), kainic acid (KA, 50%), HTL (32%), strychnine (37%), and a higher CD50 for nicotine (55%) in DBA mice. Based on these data it is suggested that pathways involving NMDA and KA receptors are responsible for increased susceptibility to seizure initiation (mEST), and are opposed by glycine pathways, and that opposing GABA and cholinergic systems at higher CNS levels are involved in seizure spread (AGSs and MEST) in these mice. Latency patterns indicate that nicotine, strychnine, PTZ and bicuculline have high blood-brain barrier (BBB) penetrability. Picrotoxin and the excitatory amino acid receptor agonists had longer latencies, suggesting low BBB penetrability. Age-related changes in latency, however, give evidence that difficulty in drug penetration of the BBB is not responsible for differences observed in CD50s between strains.
“…Thus, because anion transport systems are compromised in brain from DBA mice (Engstrom et al, 1984a), an increase in CA activity may be aimed at overcoming this defect. Also, increased CA activity may be a response to handle a greater metabolic load of C 0 2 resulting from neuronal hyperactivity in these seizuresusceptible mice.…”
Section: Chronic Actz Administration: Effects On Actz Eds0 Values Andmentioning
The clinical utility of the carbonic anhydrase (CA) inhibitor acetazolamide (ACTZ) is limited because of rapid development of tolerance to its effects. Tolerance is thought to develop as a result of glial cell proliferation and/or increased CA synthesis. DBA mice, susceptible to audiogenic seizures (AGSs) in an age-dependent manner, have increased CA activity as compared with C57 (non-audiogenic seizure susceptible) mice at 21 and 110 days of age. The present work utilized ACTZ to help determine the relationship between increased CA activity in brain and AGSs in DBA mice. Also, minimal electroshock seizure threshold (EST) was measured at various ages in DBA and C57 mice to determine age-related changes in CNS excitability. EST was significantly lower in DBA as compared with C57 mice at 18 days and between 40 and 115 days of age, suggesting that DBA mice remain hyperexcitable to electrical stimulation after they develop resistance to AGSs. ACTZ ED50s against maximal electroshock seizures (MES) were significantly higher in DBA as compared with C57 mice at 26,36, and 115 days of age. This finding correlates with higher CA activity in this strain at 110 days of age, noted previously. However, at 21 days of age, when CA activity is also higher in DBA versus C57 mice, there were no significant differences in ACTZ ED50s against MES between the strains. ACTZ ED50s against AGSs in DBA mice were considerably lower than ACTZ ED50s against MES in either strain, suggesting that a particular fraction of CA is intimately involved in the production of AGSs.(ABSTRACT TRUNCATED AT 250 WORDS)
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