POLYAMINE SIGNALING VIA GLIAL CONNEXIN-43 HEMICHANNELS IN RETINA

通过视网膜中的胶质连接蛋白 43 半通道进行多胺信号传导

• 批准号: 8167855
• 负责人: YURIY KUCHERYAVYKH
• 金额: $ 14.53万
• 依托单位: UNIVERSITY OF PUERTO RICO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167855
• 关键词: Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Connexin 43; Connexins; Data; Enzymes; Funding; Gap Junctions; Glaucoma; Glutamate Receptor; Glutamates; Grant; Institution; Intervention; N-Methyl-D-Aspartate Receptors; Neuroglia; Neurons; Photoreceptors; Physiological; Polyamines; Preparation; Research; Research Personnel; Resources; Retina; Retinal; Signal Transduction; Signaling Molecule; Source; Spermidine; Spermine; Techniques; Testing; Thick; United States National Institutes of Health; Work; excitotoxicity; ganglion cell; insight; kainate; receptor; retinal ischemia; retinal neuron

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major glial cells in the retina, M¿ller cells, span the whole retinal thickness from photoreceptors to ganglion cells. M¿ller cells contact and even delimit all neuronal compartments and can release neuroactive substances to directly regulate neurons. One likely candidate to regulate retinal neuronal activity is the endogenous polyamine spermine (SPM). The polyamines spermine and spermidine (SPM/SPD) are predominantly located in M¿ller cells in the retina, but modulate many neuronal receptors and channels found on retinal neurons including AMPA, kainate, NMDA receptor channels and Kir channels. Our preliminary data demonstrate release of SPM/SPD from this glia to neuronal network under glial specific treatments. Our working hypothesis is that endogenous SPM acts as a signaling molecule between glial and neuronal cells in the retina: (i) SPM is accumulated and released from M¿ller (glial) cells, potentially through unapposed hemi-gap junctions (hemichannels) and (ii) acts simultaneously on several types of neuronal receptors and channels to modulate retinal neuronal networks. Using electrophysiological and immunocytochemical techniques, we propose to test this hypothesis by the following specific aims: Specific aim 1 To determine if M¿ller glial cells express the biosynthetic enzymes necessary for polyamine synthesis under physiological and pathophysiological conditions. Specific aim 2  To examine SPM flux potentially through connexin hemichannels or P2X7 receptors in retinal M¿ller (glial) cells. Specific aim 3  To determine the effect of spermine on glutamate receptors in isolated retinal neurons and in a retinal whole-mount preparation. The results of these studies will provide insight into spermine-dependent retinal activity and may ultimately result in interventions for glaucoma, retinas ischemia, glutamate excitotoxicity and subsequent neuronal death.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 视网膜中的主要神经胶质细胞，m ller细胞，跨越了整个残留厚度 受感受器的神经节细胞。 m ller细胞接触甚至界定所有神经元 隔室并可以释放神经活性物质直接调节神经元。一 可能调节永久性神经元活性的候选者是内源性多胺精子 （SPM）。多胺的精子和精子（SPM/SPD）主要位于 视网膜中的m ller细胞，但调节许多神经元接收器和通道 包括AMPA，Kainate，NMDA受体通道和KIR通道在内的视网膜神经元。我们的 初步数据表明，SPM/SPD从该神经胶质到神经元网络的释放 神经胶质特定治疗。我们的工作假设是内源性SPM充当信号 视网膜中神经胶质细胞和神经元细胞之间的分子：（i）SPM积累并释放 从M ller（神经胶质）细胞，可能通过未应用的半间隙连接（半通道） （ii）仅对几种类型的神经元接收器和通道进行调节 视网膜神经元网络。使用电生理和免疫细胞化学技术， 我们建议通过以下特定目的检验这一假设： 具体目标1以确定M ller神经胶质细胞是否表达必要的生物合成酶 在生理和病理生理条件下多胺合成。 特定的目标2可以通过连接蛋白半通道或P2X7检查SPM通量 视网膜ller（神经胶质）细胞中的受体。 具体目标3以确定亚精素对分离的谷氨酸受体的影响 视网膜神经元和永久整体准备。 这些研究的结果将为精子依赖性视网膜活性和 最终可能导致青光眼，视网膜缺血，谷氨酸的干预措施 兴奋性毒性和随后的神经元死亡。