NPY suppresses seizures and modulates thalamocortical activity in animal models of generalized epilepsy

NPY 在全身性癫痫动物模型中抑制癫痫发作并调节丘脑皮质活动

• 批准号: nhmrc : 400106
• 负责人: A/Pr Christopher Reid
• 金额: $ 25.74万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/npy-suppresses-seizures-generalized-epilepsy/100556
• 关键词: NPY; suppresses; seizures; modulates; thalamocortical

Epilepsy is the most common serious chronic neurological disease in the community, affecting up to 3% of the population in a lifetime and 0.5-1% at any one time. Absence epilepsy is one of the most common types of epilepsy, most frequently seen in childhood and teenage years that may persist into adulthood. Anti-epileptic drugs are effective in controlling absence seizures in most patients, however there is an important group (20-40%) of patients in whom the absence seizures remain uncontrolled with current medications. Recently there has been considerable interest in the role that chemical in the brain, such as neuropeptide Y (NPY), may play in epilepsy. The research proposed will examine the role of NPY in several animal models of absence epilepsy. We have recently shown that NPY suppresses absence seizures in a rat genetic model of generalised epilepsy, and that this appears to be mediated by Y2 receptors. This work will build on these novel findings, and determine the localisation of the effect within the brain, and the underlying mechanism. We will check NPY effects across several models in different species, a genetic rat model with spontaneous seizures, and in mice treated with a chemical to induce seizures. This will determine its broad applicability. We will also determine the effects of removal of NPY or NPY receptors on the effects of NPY on seizure expression. Finally, brain recording techniques will be applied to determine the mechanism and site within the brain underlying the protective actions of NPY. The project has the potential to provide novel insights into the role of NPY in the expression and modulation of absence seizures. NPY related mechanisms might represent targets for the development of a new class of therapeutic agents for the treatment of absence epilepsy. Targets that are identified as being important in the expression of absence seizures may also prove to be relevant in other types of generalised epilepsy syndromes.

癫痫是社区中最常见的严重慢性神经系统疾病，一生中影响高达 3% 的人口，任何时候影响 0.5-1%。失神癫痫是最常见的癫痫类型之一，最常见于儿童和青少年时期，可能持续到成年。抗癫痫药物可有效控制大多数患者的失神发作，但有一个重要群体 (20-40%) 的患者目前的药物治疗仍无法控制失神发作。最近，人们对大脑中的化学物质（例如神经肽 Y (NPY)）在癫痫中可能发挥的作用产生了相当大的兴趣。拟议的研究将检验 NPY 在几种失神性癫痫动物模型中的作用。我们最近表明，NPY 可抑制大鼠全身性癫痫遗传模型中的失神发作，并且这似乎是由 Y2 受体介导的。这项工作将建立在这些新发现的基础上，并确定大脑内效应的定位以及潜在的机制。我们将检查 NPY 在不同物种的几种模型中的效果，包括自发性癫痫发作的遗传大鼠模型，以及用化学物质治疗诱发癫痫发作的小鼠。这将决定其广泛的适用性。我们还将确定去除 NPY 或 NPY 受体对 NPY 对癫痫发作表达的影响。最后，将应用大脑记录技术来确定 NPY 保护作用的大脑机制和部位。该项目有可能为 NPY 在失神发作的表达和调节中的作用提供新的见解。 NPY 相关机制可能代表开发一类新型治疗失神性癫痫药物的目标。被认为在失神发作表达中重要的目标也可能被证明与其他类型的全身性癫痫综合征相关。