GLIAL CELLS AND SYNAPTIC REMODELING

胶质细胞和突触重塑

• 批准号: 2266587
• 负责人: SCOTT Loren POMEROY
• 金额: $ 18.77万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2266587
• 关键词: age difference; autonomic ganglion; axon; cell cycle; developmental neurobiology; gene expression; glia; growth factor receptors; immunocytochemistry; intercellular connection; laboratory mouse; mitogens; neural plasticity; platelet derived growth factor; polymerase chain reaction; synapses; video microscopy

The long-term objective of this project is to determine how glial cells effect changes in synaptic connections. In parasympathetic ganglia, synapses cluster near the nucleus of glia called satellite cells. This relationship is retained as both synapses and satellite cells undergo. rearrangements over time, suggesting that these glia have a role in the maintenance of synapses and that they may participate in synaptic remodeling. The research described here examines this relationship with 3 objectives. The first objective is to determine how satellite cells are added postnatally to neurons. The addition of glia will be measured using quantitative light microscopy. Bromodeoxyuridine immunohistochemistry will be used to explore whether mitosis accounts the addition of glia. To determine if they arise from cells associated with neurons, the fate of individual satellite cells labeled with intracellular dextran-- rhodamine will be monitored by repeated examination with in vivo video microscopy. The second objective is to establish the function of platelet-growth factor (PDGF) in regulating the proliferation of satellite cells after axotomy of their associated neurons. PDGF is present in many neurons and mitogenic to glia. Following axotomy of the superior cervical ganglion, changes of gene expression for PDGF and its receptor will be monitored using the polymerase chain reaction. It will then be determined whether the proliferative response is blocked with antibodies against PDGF and its receptor. The third objective links satellite cell proliferation to synaptic remodeling. It will be determined by direct observation with in vivo microscopy whether synaptic remodeling continues in older mice when satellite cell number no longer increases, and whether synaptic remodeling is induced when satellite cells are stimulated to divide. These experiments are designed to explore how glial cells elicit changes in synaptic connections. They will provide insights as to how the nervous system responds to injury. Furthermore, the understanding of how glial cells bring about synaptic change is directly relevant to the normal development of the nervous system and to disorders arising from abnormal development.

该项目的长期目标是确定神经胶质细胞 突触连接的效果变化。 在副交感神经中， 突触簇在神经胶质细胞核附近，称为卫星细胞。 这 随着突触和卫星细胞的经历，关系被保留。 随着时间的推移重新排列，表明这些神经胶质在 维持突触，并可能参与突触 重塑。 这里描述的研究研究了与 3个目标。 第一个目标是确定如何添加卫星细胞 产后到神经元。 Glia的添加将使用 定量光学显微镜。 溴脱氧尿苷免疫组织化学 将用于探索有丝分裂是否说明神经胶质的添加。 为了确定它们是否来自与神经元相关的细胞，命运 用细胞内葡萄糖标记的个体卫星细胞 - Rhodamine将通过体内视频重复检查来监测 显微镜。 第二个目标是建立血小板增长的功能 调节卫星细胞增殖的因子（PDGF） 其相关神经元的轴突切开术。 PDGF存在于许多神经元中，并且 促粒神经胶质的有丝分裂。 在上颈神经节的轴切开后， PDGF及其受体的基因表达的变化将受到监测 使用聚合酶链反应。 然后将确定是否 用抗PDGF的抗体阻止增生反应，并 它的受体。 第三个目标链接卫星细胞增殖与突触 重塑。 它将通过体内直接观察来确定 显微镜检查在老鼠时是否在年龄较大的小鼠中继续 卫星细胞编号不再增加，并且是否突触 当刺激卫星细胞分裂时，会诱导重塑。 这些实验旨在探索神经胶质细胞如何引起变化 在突触连接中。 他们将提供有关如何 神经系统应对伤害。 此外，对如何理解 神经胶质细胞带来突触变化与 神经系统的正常发育以及因 异常发展。

项目成果

Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas.

• 发表时间: 1999-02
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: John Y. H. Kim;M. Sutton;Diane J. Lu;Tracey A. Cho;L. Goumnerova;Lyuda Goritchenko;Jill R. Kaufman;K. Lam;A. Billet;N. Tarbell;Julian Wu;J. Allen;C. Stiles;R. Segal;S. Pomeroy

Trk receptors function as rapid retrograde signal carriers in the adult nervous system.

Trk 受体在成人神经系统中充当快速逆行信号载体。

• DOI: 10.1523/jneurosci.17-18-07007.1997
• 发表时间: 1997
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Bhattacharyya,A;Watson,FL;Bradlee,TA;Pomeroy,SL;Stiles,CD;Segal,RA
• 通讯作者: Segal,RA