SEXUAL DIMORPHISM IN SEIZURE CONTROL

描述：类固醇激素调节对正常大脑至关重要 发展，并可能在人类癫痫发作障碍中发挥重要作用。 的 黑质网状部（SNR）是控制 癫痫活动通过GABA能神经传递扩散 尤其是通过GABAA受体。 SNR在功能上细分为 调节蝇蕈醇（A）的相反作用的前部和后部区域 GABAA受体激动剂）对氟乙基癫痫发作的影响。 蝇蕈醇输注 SNRantere产生抗惊厥作用，而类似的输注在 SNRposterior产生促惊厥作用。 初步数据显示， 这两个SNR区域的功能成熟可能是在性腺类固醇激素的作用下 荷尔蒙控制 在卵巢去势雄性大鼠中， “抗惊厥药”SNRanterior的成熟。 新生儿阉割 不影响“促惊厥”SNR区域的出现。 此外，委员会认为， 在雌性大鼠中，SNR没有功能分离，因为 蝇蕈醇输注产生抗惊厥作用，与注射无关 绝佳的价钱 因此，在生命早期睾丸激素的存在可能是 负责SNR的功能分离。 以下 假设将进行测试：在雄性大鼠中，出生后早期消耗 睾丸激素加速“抗惊厥药”SNRanterior的发展 地区 在雄性大鼠中，“促惊厥”的SNRposterior 区域是独立的出生后早期睾酮。 两个SNR区域 具有与两个SNR区域相似的特征 正常雄性大鼠（术语特征表示对GABA能试剂的反应性 输出网络）。 缺乏产前睾丸激素会导致女性 仅具有一个GABAA敏感SNR区域的SNR类型。 女间谍 可能与成熟的男性“抗惊厥药”SNRanterior有相似的特征。 产前睾丸激素激增是导致 “促惊厥”SNR区域。 方法包括产后早期阉割， 激素替代，局部输注GABAA激动剂和拮抗剂， 氟乙基癫痫发作试验和[14C]脱氧葡萄糖放射自显影。 大鼠 将使用不同性别和不同年龄的人。 这些研究可能会导致 开发新的抗癫痫治疗方法， 年龄相关的性别差异。

DESCRIPTION: Steroid hormonal regulation is critical for normal brain development and may play an important role in human seizure disorders. The substantia nigra pars reticulata (SNR) is one of the structures controlling the spread of seizure activity via its GABAergic neurotransmission especially through GABAA receptors. The SNR is functionally subdivided into anterior and posterior regions which mediate opposing effects of muscimol (a GABAA receptor agonist) on fluorothyl seizures. Muscimol infusions in the SNRanterior produce anticonvulsant effects, while similar infusions in the SNRposterior produce proconvulsant effects. Preliminary data show that the functional maturation of these two SNR regions may be under gonadal steroid hormonal control. In neonatally castrated m ale rats there is accelerated maturation of the "anticonvulsant" SNRanterior. Neonatal castration does not influence the emergence of the "proconvulsant" SNR region. Furthermore, in female rats there is no functional segregation of the SNR because muscimol infusions produce anticonvulsant effects irrespective to injection site. Therefore, the presence of testosterone early in life may be responsible for the functional segregation of the SNR. The following hypotheses will be tested: In male rats, early postnatal depletion of testosterone accelerates the development of the "anticonvulsant" SNRanterior region. In male rats, the emergence of the "proconvulsant" SNRposterior region is independent of early postnatal testosterone. The two SNR regions in neonatally castrated rats have similar features as the two SNR regions in normal male rats (the term features denotes responsivity to GABAergic agents and output networks). Lack of prenatal testosterone leads to the female type of the SNR with only one GABAA sensitive SNR region. The female SNR may have similar features with the mature male "anticonvulsant" SNRanterior. The prenatal testosterone surge is responsible for the development of the "proconvulsant" SNR region. Methods include early postnatal castration and hormone replacements, localized infusions of GABAA agonists and antagonists, flurothyl seizure testing and [14C] deoxyglucose autoradiography. Rats of both sexes and various ages will be used. These studies may lead to the development of new antiepileptic treatments that take into the account sexual age-related differences.