MOLECULAR BIOLOGIC BASIS OF KINDLING

Kindling 的分子生物学基础

• 批准号: 3901572
• 负责人: S NADI
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3901572
• 关键词: enzyme mechanism; gene expression; glutamate decarboxylase; glutamate receptor; human tissue; in situ hybridization; laboratory rat; messenger RNA; molecular pathology; neurochemistry; neuropeptides; neurotransmitter metabolism; partial seizure; somatostatin; tyrosine 3 monooxygenase

Previous work from our laboratory has demonstrated a time dependent change in the levels of somatostatin in the cortex and hippocampus of the kindled rat brain. In addition, the activity of tyrosine hydroxylase is increased immediately following a seizure. Glutamate decarboxylase levels were not found to be changed in any stage of the kindled rat brain. In view of the fact that some regulatory DNA such as c-fos are altered in the seizure state, it was of interest to undertake a study of the expression of the mRNA for somatostatin, tyrosine hydroxylase and glutamate decarboxylase and their correlation with the expression of the c-fos gene to determine if c-fos regulates the levels of expression of the above-mentioned compounds. Currently the above studies are being expanded to incorporate the time course of the development of mRNA alterations and additional investigations of blocking of seizures on the expression of the mRNA are being undertaken. Long-term studies include the in situ hybridization studies of the human epileptic focus and comparing it to the nonfocal tissue from the same patient. These studies will help determine the phase of the seizure progression when the mRNA changes occur. Such observations will help understand how the expression of genes is influenced in the situation where increased spiking activity occurs in the brain. Such an understanding of the kindled brain may help in elucidating the long-term changes which occur in the human epileptic focus. Similarly studies are ongoing to correlate the changes in amino acid transmitters, neuropeptides, enzymes and receptors with the development of seizures.

我们实验室以前的工作已经证明了一个依赖于时间的变化 在点燃的大脑皮层和海马体中生长抑素的水平 老鼠大脑。 此外，酪氨酸羟化酶的活性增加 在癫痫发作后立即发作。 谷氨酸脱羧酶水平没有 发现在点燃的大鼠大脑的任何阶段都发生了变化。 考虑到 事实上，一些调控DNA如c-fos在癫痫发作中发生了改变， 因此，有必要研究《公约》的表达方式， 生长抑素、酪氨酸羟化酶和谷氨酸脱羧酶的mRNA， 它们与c-fos基因表达的相关性，以确定是否 c-fos调节上述化合物的表达水平。 目前，上述研究正在扩大， mRNA变化的发展过程和其他研究 阻断癫痫发作对mRNA表达的影响。 长期的研究包括人类的原位杂交研究， 癫痫灶，并将其与来自相同癫痫灶的非病灶组织进行比较。 病人 这些研究将有助于确定癫痫发作进展的阶段， mRNA发生了变化。 这样的观察将有助于理解 基因的表达受到影响的情况下， 活动发生在大脑中。 如此理解被点燃的大脑 可能有助于阐明人类发生的长期变化， 癫痫灶 类似的研究正在进行中，以关联氨基酸的变化， 神经递质、神经肽、酶和受体， 癫痫发作。