AGRIN AND INTEGRIN EXPRESSION IN LEARNING AND LTP

学习和 LTP 中的 AGRIN 和整合素表达

• 批准号: 6346169
• 负责人: EDWIN J BAREA-RODRIGUEZ
• 金额: $ 14.87万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346169
• 关键词: NMDA receptors; agrin; gene expression; hippocampus; in situ hybridization; integrins; laboratory rat; learning; long term potentiation; messenger RNA; neural plasticity; neuroanatomy; opioid receptor; polymerase chain reaction; protein structure function; space perception; synapses; western blottings

Since changes in synaptic morphology are observed in learning and long- term potentiation, proteins known to contribute to the stability of synaptic contacts are of particular interest to understand memory functions. The overall goal is to investigate mRNA expression of agrin and integrins, and the factors that may mediate their expression in the rat hippocampus during long-term potentiation and spatial learning. Agrins and integrins are extracellular matrix proteins that may play an important role in synaptogenesis and the modification of existing synapses. Both morphological changes and/or synaptogenesis have been observed in learning and long-term potentiation. Preliminary studies find that again mRNA expression is induced in the brain of animals during learning a spatial navigational task. We have evidence also that agrin mRNA is expressed with hippocampal long-term potentiation. The hippocampus displays t least two forms of synaptic plasticity, one that requires the activation of the glutaminergic receptor displays at least two forms of synaptic plasticity, one that requires the activation of the glutaminergic receptor N-Methyl-D-Aspartate (NMDA) and another that requires the activation of opiodergic receptors. Opioids are found in the lateral perforant path to area CA3, the lateral perforant path to dentate gyrus, and the mossy fiber to area CA3. Thus gene expression may be modulated by the activation of NMDA and opioid receptors. Agrin and integrin mRNA expression during long-term potential will be investigated in the perforant path-dentate gyrus and the perforant path-CA3 pathways using awake freely-moving rats. These pathways expressed NMDA and opioid- receptor dependent long-term potentiation. Specific Aim 1 will investigate temporal mRNA expression of agrin and integrins during long-term potentiation. Naloxone and selective opioid or NMDA receptor antagonists will be used to investigate if the activation of opioid or NMDA receptors is involved in agrin or integrins mRNA expression. Specific Aim 2 will investigate the time course induction of agrin during spatial learning of the Morris water maze task. Naloxone and selective opioid receptor and NMDA receptor antagonists will be used to investigate if the activation of opioid or NMDA receptors is involved in agrin or integrins mRNA expression during this form of learning. These studies will investigate also if the impairment in learning observed with the administration of opioid or NMDA receptor antagonists parallel the blockade of agrin and integrin mRNA expression.

由于在学习和长时程增强过程中可以观察到突触形态的变化，因此已知有助于突触接触稳定性的蛋白质对于理解记忆功能具有特别的意义。本研究的目的是研究长时程增强和空间学习过程中大鼠海马中agrin和整合素的mRNA表达及其介导因素。重组蛋白和整合素是细胞外基质蛋白，可能在突触发生和现有突触的修饰中发挥重要作用。在学习和长时程增强过程中观察到形态学变化和/或突触发生。初步研究发现，在学习空间导航任务的过程中，动物大脑中再次诱导mRNA的表达。我们也有证据表明，agrin mRNA的表达与海马长期增强。海马至少表现出两种形式的突触可塑性，一种需要激活谷氨酰胺能受体，一种需要激活谷氨酰胺能受体n -甲基- d -天冬氨酸（NMDA），另一种需要激活阿片能受体。在CA3区侧穿道、齿状回侧穿道和CA3区苔藓纤维中发现了阿片样物质。因此，基因表达可能通过NMDA和阿片受体的激活来调节。我们将使用清醒的自由运动大鼠，研究长期电位期间穿孔通路-齿状回和穿孔通路- ca3通路中Agrin和整合素mRNA的表达。这些通路表达NMDA和阿片受体依赖的长期增强。特异性目的1将研究长时程增强过程中agrin和整合素的时间mRNA表达。纳洛酮和选择性阿片或NMDA受体拮抗剂将用于研究阿片或NMDA受体的激活是否参与agrin或整合素mRNA的表达。专项目的2将研究Morris水迷宫任务空间学习过程中agrin的时间过程诱导。纳洛酮和选择性阿片受体和NMDA受体拮抗剂将用于研究在这种学习形式中，阿片受体或NMDA受体的激活是否参与了agrin或整合素mRNA的表达。这些研究还将调查阿片类药物或NMDA受体拮抗剂是否与阻断agrin和整合素mRNA表达平行，从而观察到学习障碍。