MOLECULAR BIOLOGIC BASIS OF KINDLING

Kindling 的分子生物学基础

• 批准号: 3922597
• 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/3922597
• 关键词: DNA; biological polymorphism; complementary DNA; enzyme mechanism; gene expression; generalized seizures; glutamate decarboxylase; glutamate receptor; human tissue; in situ hybridization; inborn metabolism disorder; laboratory rat; messenger RNA; neurochemistry; neuropeptides; neurotransmitter metabolism; nucleic acid hybridization; 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 glutamine 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 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表明， 皮质和海马生长抑素水平的变化 点燃的老鼠大脑。 此外，酪氨酸的活性 羟化酶在癫痫发作后立即增加。 谷氨酸脱羧酶水平没有发现任何变化， 点燃的大鼠大脑的阶段。 鉴于有些人 调控DNA如c-fos在癫痫发作状态下发生改变， 有兴趣进行mRNA表达的研究， 生长抑素、酪氨酸羟化酶和谷氨酰胺脱羧酶 以及与c-fos基因表达的相关性， 确定c-fos是否调节上述的表达水平- 提到的化合物。 目前，上述研究正在扩大，以纳入 mRNA变化的发展时间过程和额外的 阻断癫痫发作的研究 mrna正在进行中。 长期研究包括现场 人类癫痫灶的杂交研究及比较 与同一患者的非病灶组织接触。 这些研究将有助于确定癫痫发作的阶段 当mRNA发生变化时就会进展。 这些观察将 有助于了解基因的表达是如何影响 在这种情况下，大脑中的尖峰活动增加。 对被点燃的大脑的这种理解可能有助于阐明 人类癫痫病灶的长期变化。 类似的研究正在进行中，以关联氨基酸的变化， 酸递质、神经肽、酶和受体， 发展癫痫。