tetracycline and Epilepsy

A major goal of epilepsy research is to understand the molecular and functional basis of seizure genesis. A human GABA(A) gamma2 gene mutation (R43Q) is associated with generalized epilepsy. Introduction of this mutation into a mouse by gene targeting recapitulates the human phenotype demonstrating a strong genotype to phenotype link. GABA(A) receptors play a role in the moment-to-moment control of brain function and also on the long-term wiring of the brain by directing neuronal development. Our objective was to determine whether developmental expression of the mutation alters seizure susceptibility later in life.. A tetracycline-based conditional model for activation of a hypomorphic Q43 disease allele was created and validated. Seizure susceptibility was assessed using the subcutaneous pentylenetetrazole model.. Seizure susceptibility was significantly reduced in mice where the Q43 allele was suppressed during development.. These results demonstrate that a human epilepsy-causing mutation impacts network stability during a critical developmental period. These data suggest that identification of presymptomatic children may provide a window for therapeutic intervention before overt symptoms are observed, potentially altering the course of epileptogenesis.

Topics: Animals; Brain; Brain Chemistry; Convulsants; Disease Models, Animal; Epilepsy; gamma-Aminobutyric Acid; Genetic Predisposition to Disease; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Nerve Net; Neural Inhibition; Pentylenetetrazole; Receptors, GABA-A; Tetracycline

Topics: Carbimazole; Chlorpromazine; Diabetes Mellitus; Diazepam; Drug Prescriptions; Epilepsy; Female; Fetus; Heparin; Humans; Hyperthyroidism; Infant, Newborn; Insulin; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Smoking; Streptomycin; Tetracycline; Warfarin

Topics: Actinomyces; Actinomycosis; Adult; Biopsy; Bronchial Neoplasms; Cephalosporins; Dental Caries; Epilepsy; Female; Humans; Lung Diseases; Male; Middle Aged; Periostitis; Radiography; Tetracycline

Topics: Adolescent; Adult; Ampicillin; Anemia, Hemolytic; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Diarrhea; Drug Eruptions; Epilepsy; Erythromycin; Female; Hepatic Encephalopathy; Humans; Hyperkalemia; Kanamycin; Lincomycin; Male; Middle Aged; Penicillins; Potassium; Sodium; Tetracycline