EPILEPTOGENESIS IN THE AGED CNS

描述：（改编自应用程序）虽然流行病学 研究表明癫痫发作的发病率和患病率增加 在老年人的疾病中，潜在的机制尚不清楚。 目标 这个项目的目的是研究生理机制， 导致了癫痫 将使用老年啮齿动物作为模型 由于几项研究表明， 老化过程中的敏感性。 申请人的初步研究 证实了这些发现，并表明，增加的倾向， 产生癫痫样活动也可以在神经元组织中看到， 在暴露于GABA-A受体拮抗剂后分离。 这表明 在衰老过程中，中枢神经系统可能发生变化，这可能是 增加癫痫发作的敏感性。 将检查齿状回， 它被认为在某些形式的癫痫中起关键作用， 老年齿状回的解剖学变化已经被描述， 会引起癫痫 他们的主要假设是， 复发性兴奋和/或抑制是癫痫发作增加的基础 老年CNS的易感性。 他们还将检查是否有变化 可能与非突触机制有关。 几种电生理技术将被用来测试这两个 老年大鼠的假设 将进行细胞内和细胞外记录 以检测是否存在新的复发性兴奋性 电路和检查突触抑制的强度。 细胞外 将在低[Ca 2 +]o和高[K+]o培养基中进行记录， 氨基酸受体拮抗剂，以确定是否有增加的 老年大鼠齿状回非突触性癫痫发作的易感性。 将进行解剖学研究，以评价轴突的变化。 详细说明。 这些实验应该开始解决突触重组是否 和/或改变的非突触相互作用是癫痫发作增加的基础 老年人的易感性。 长期目标之一是 了解老年人癫痫发生的机制，使患者 可以得到更有效的诊断和治疗。 此外，Synaptic 重组也可能影响海马体的其他过程， 和记忆 因此，通过检查老年中枢神经系统内的突触重组， 它们还可以提供对癫痫基本机制的深入了解， 学习和记忆的能力。

DESCRIPTION: (Adapted from the application) Although epidemiological studies have demonstrated an increased incidence and prevalence of seizure disorders in the elderly, the underlying mechanisms are not known. The goal of this project is to investigate physiological mechanisms that could contribute to this epileptogenicity. Aged rodents will be used as the model system since several studies suggest a similar increase in seizure susceptibility during aging. The applicant s preliminary studies corroborate these findings and demonstrate that an increased propensity to generate epileptiform activity can also be seen in neuronal tissue in isolation following exposure to a GABA-A receptor antagonist. This suggests that alterations may occur in the CNS during aging that could underlie an increased seizure susceptibility. The dentate gyrus will be examined since it is believed to play a critical role in some forms of epilepsy and anatomical changes have been described in the aged dentate gyrus that could be epileptogenic in nature. Their primary hypothesis is that changes in recurrent excitation and/or inhibition underlie the increased seizure susceptibility in the aged CNS. They will also examine whether alterations in nonsynaptic mechanisms may be involved. Several electrophysiological techniques will be used to test these two hypotheses in aged rats. Intra- and extracellular recordings will be made from granule cells to test for the presence of new recurrent excitatory circuits and to examine the strength of synaptic inhibition. Extracellular recordings will be made in low [Ca2+]o and elevated [K+]o media containing amino acid receptor antagonists to determine if there is an increased susceptibility to generate nonsynaptic seizures in the dentate of aged rats. Anatomical studies will be performed to evaluate changes in axonal elaboration. These experiments should begin to address whether synaptic reorganization and/or altered nonsynaptic interactions underlie the increased seizure susceptibility in the elderly. One of the long-term objectives is to understand the mechanisms of epileptogenesis in the elderly so that patients can be diagnosed and treated more effectively. Additionally, synaptic reorganization may also affect other hippocampal processes such as learning and memory. Thus, by examining synaptic reorganization within the aged CNS they may also provide insight into the basic mechanisms of epilepsy and learning and memory within the overall population.