Evidence for an extended duration of GABA-mediated excitation in the developing male versus female hippocampus

التفاصيل البيبلوغرافية
العنوان: Evidence for an extended duration of GABA-mediated excitation in the developing male versus female hippocampus
المؤلفون: Joseph L. Nuñez, Margaret M. McCarthy
المصدر: Developmental neurobiology. 67(14)
سنة النشر: 2007
مصطلحات موضوعية: Agonist, Male, medicine.medical_specialty, Time Factors, Calcium Channels, L-Type, medicine.drug_class, GABA Agents, Sodium-Potassium-Chloride Symporters, Biology, Hippocampal formation, Hippocampus, gamma-Aminobutyric acid, Calcium in biology, Article, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Calcium imaging, Developmental Neuroscience, Internal medicine, medicine, Animals, Solute Carrier Family 12, Member 2, Cells, Cultured, gamma-Aminobutyric Acid, Neurons, Sex Characteristics, Voltage-dependent calcium channel, Symporters, GABAA receptor, Muscimol, Age Factors, Gene Expression Regulation, Developmental, CREB-Binding Protein, Rats, Endocrinology, chemistry, nervous system, Calcium, Female, medicine.drug
الوصف: γ-Aminobutyric acid (GABA) is as an excitatory neurotransmitter during brain development. Activation of GABAA receptors in neonatal rat hippocampus results in chloride efflux and membrane depolarization sufficient to open voltage sensitive calcium channels. As development progresses, there is a decline in the magnitude of calcium influx subsequent to GABAA receptor activation and the number of cells that respond to GABA with excitation. By the second postnatal week in the rat, GABA action in the hippocampus is predominantly inhibitory. The functional consequences and endogenous regulation of developmental GABA-mediated excitation remains under-explored. Hippocampal neurons in the newborn male and female rat respond to GABAA receptor activation with increased intracellular calcium and are susceptible to GABA-mediated damage – both being indicative of the excitatory nature of GABA. In the present study we observed that by postnatal day 7, only males are susceptible to GABAA agonist-induced damage and respond to GABAA agonist administration with elevated levels of intracellular calcium in cultured hippocampal neurons. By postnatal day 14, GABAA agonist administration was without effect on intracellular calcium in both males and females. The age-related sex difference in the impact of GABAA receptor activation correlates with a sex difference in chloride co-transporter expression. Males have elevated protein levels of pNKCC1 on PN0 and PN7, with no sex difference by PN14. In contrast, females displayed elevated levels of KCC2 on PN7. This converging evidence infers that sex affects the duration of GABAA receptor-mediated excitation during normal hippocampal development, and provides a mechanism by which the effect is mediated. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
تدمد: 1932-8451
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28e6ec0283963ec62b347346755b5cd3Test
https://pubmed.ncbi.nlm.nih.gov/17823921Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....28e6ec0283963ec62b347346755b5cd3
قاعدة البيانات: OpenAIRE