Afferent influences: cell death in n. magnocellularis

传入影响：n中的细胞死亡。

• 批准号: 6405509
• 负责人: BRANDY L WILKINSON
• 金额: $ 2.41万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6405509
• 关键词: BCL2 gene /protein; afferent nerve; apoptosis; auditory nuclei; cell death; chickens; cytochrome c; denervation; developmental neurobiology; immunocytochemistry; in situ hybridization; mitochondria; neurons; predoctoral investigator; western blottings

Neuronal survival in developing animals is often dependent on afferent activity. In the posthatch chick, elimination of eighth nerve activity leads to the death of 20-40% of the neurons in the cochlear nucleus, nucleus magnocellularis (NM). The factors that determine whether an individual NM neuron will live or die are largely unknown. Previous studies indicate that both cell death and cell survival mechanisms compete to determine an individual cell's fate. This proposal seeks to examine the underlying cellular and molecular cascades that are activated following deafferentation. Several studies have implicated bcl-2 family members in the regulation of common cell death pathways. This gene family includes both cell "protectors" (bcl-2 and bcl-xL) and "executioners" (bax and bak). The effect of deafferentation on the activation and expression of pro-survival bcl-2 gene and gene product will be examined using both in situ hybridization and immunocytochemistry. Additional studies will be performed to assess the effect of deafferentation on other members of the bcl-2 family. For example, pro-apoptotic bax will be investigated for differential expression from the pro-survival bcl-2 protein. Another line of research will focus on molecules thought to participate in apoptosis downstream of bcl-2 genes. Mitochondrial integrity is pivotal to the maintenance of healthy cells; compromise of mitochondrial bioenergetics can result in the release of cytochrome-c. Cytosolic cytochrome-c activates what is commonly referred to as the apoptosome. This complex of molecules including cytochrome-c, Apaf-1, and caspase-9 will initiate proteolytic caspase cascades that ultimately lead to cell death. Afferent regulation of all the molecules involved in the apoptosome will be investigated through a combination of immuncytochemistry and Western blotting techniques. It is the hope that this research will elucidate some of the underlying mechanisms involved with deafferentation-induced cell death.

发展动物的神经元存活通常取决于传入活性。在后雏鸡中，消除第八神经活性导致在耳蜗核，核细胞核（NM）中20-40％的神经元死亡。决定单个NM神经元是否生存还是死亡的因素在很大程度上未知。先前的研究表明，细胞死亡和细胞存活机制都竞争确定单个细胞的命运。该提案旨在检查脱落后激活的基本细胞和分子级联反应。几项研究已暗示BCL-2家族成员在调节常见细胞死亡途径中。该基因家族包括细胞“保护剂”（BCL-2和BCL-XL）和“ executioners”（Bax和Bak）。使用原位杂交和免疫细胞化学化学，将检查脱efterentation对促生存BCl-2基因和基因产物激活和表达的影响。将进行其他研究，以评估剥离对Bcl-2家族其他成员的影响。例如，将研究促凋亡的Bax，以供促生物育种的Bcl-2蛋白质差异表达。另一项研究将集中于被认为参与Bcl-2基因下游凋亡的分子。线粒体完整性对于维持健康细胞至关重要。线粒体生物能的妥协可能导致细胞色素-C的释放。胞质细胞色素-C激活通常称为凋亡小体的。这种分子的复合物在内，包括细胞色素-C，APAF-1和caspase-9将启动蛋白水解caspase cascades，最终导致细胞死亡。通过免疫化学和蛋白质印迹技术的结合，将研究对圆顶体涉及的所有分子的传入调节。希望这项研究能够阐明与脱附导致细胞死亡有关的一些基本机制。