Effects of Age on ERK and CREB Protein in Learning

年龄对学习中 ERK 和 CREB ​​蛋白的影响

• 批准号: 6876822
• 负责人: JULISSA S VILLARREAL
• 金额: $ 3.26万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-15 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876822
• 关键词: animal old age; behavior test; behavioral /social science research tag; cAMP response element binding protein; conditioning; fear; immature animal; laboratory rat; learning; memory; memory disorders; mitogen activated protein kinase; phosphorylation; psychological aspect of aging

Understanding the behavioral and molecular changes that occur with normal aging is important in studying age-related cognitive dysfunction not associated with any neuropathological diseases. Neuron counts, number of synapses, and the biophysical properties of neurons have all been investigated in the brains of aged rodents, nonhuman primates, and humans, to determine if changes in these areas cause memory deficits during aging. Thus far, there does not seem to be significant changes in these areas that would explain these memory deficits. Other studies have investigated the levels of specific proteins such protein kinase C and synaptic proteins of young and aged rats in order to explain age-related memory deficits. Most of the studies have used the Morris water maze spatial task, a task known to be hippocampally-associated. However, the hippocampus is also important in processing temporally discontiguous stimuli in tasks such as trace fear conditioning. In trace fear conditioning, the subject learns to associate a neutral conditioned stimulus (CS) and an aversive unconditioned stimulus (US) with a silent "trace interval" existing between the CS and US. The long term goal of this application is to investigate the protein expression of extracellular-signal regulated kinases (ERK) and cAMP responsive element binding (CREB) proteins in young and aged rats trained in trace fear conditioning as well as the importance of ERK in trace fear conditioning. In Specific Aim 1, experiments will investigate whether aged rats are impaired in trace fear conditioning. In Specific Aim 2A, experiments will investigate whether ERK protein expression is altered in aged rats trained in trace fear conditioning. In Specific Aim 2B, experiments will investigate whether CREB protein expression is altered in aged rats trained in trace fear conditioning. In Specific Aim 3, experiments will the effects of ERK inhibition on learning and CREB phosphorylation in young rats trained in trace fear conditioning. The central hypothesis is that aged rats are impaired in trace fear conditioning because of altered levels of ERK and CREB proteins. These studies are expected to increase our knowledge of the cellular and molecular mechanisms that may underlie age-related deficits in learning and memory. Such an outcome is expected to benefit our understanding of how normal aging affects learning and memory processes.

了解正常衰老的行为和分子变化对于研究与任何神经病理疾病无关的年龄相关认知功能障碍很重要。在老年啮齿动物，非人类灵长类动物和人类的大脑中，已经研究了神经元计数，突触的数量和神经元的生物物理特性，以确定这些区域的变化是否会导致衰老期间记忆缺陷。到目前为止，这些领域似乎没有重大变化可以解释这些记忆缺陷。其他研究研究了特异性蛋白质的水平此类蛋白激酶C和年龄大鼠的突触蛋白，以解释与年龄相关的记忆缺陷。大多数研究都使用了莫里斯水迷宫的空间任务，该任务已知是与海马相关的。但是，海马在处理诸如痕量恐惧调节之类的任务中的时间不连续刺激方面也很重要。在痕量恐惧条件下，受试者学会将中性条件刺激（CS）和厌恶无条件的刺激（US）与CS和我们之间存在的无声“痕量间隔”相关联。该应用的长期目标是研究年轻大鼠和年龄大鼠在痕量恐惧调节中训练的年轻大鼠和老年大鼠的细胞外信号调节激酶（ERK）和cAMP反应性元件结合（CREB）蛋白的蛋白质表达，以及ERK在痕量中的重要性恐惧条件。在特定的目标1中，实验将研究在痕量恐惧条件下是否会损害老年大鼠。在特定的目标2a中，实验将研究在训练有素的恐惧调节的老年大鼠中ERK蛋白表达是否改变。在特定的目标2b中，实验将研究在接受痕量恐惧调节的老年大鼠中CREB蛋白表达是否改变。在特定的目标3中，实验将ERK抑制对接受痕量恐惧条件训练的年轻大鼠学习和CREB磷酸化的影响。中心假设是，由于ERK和CREB蛋白水平改变，老化的大鼠在痕量恐惧调节中受到了损害。这些研究有望增加我们对可能与年龄相关的学习和记忆缺陷构成的细胞和分子机制的了解。期望这样的结果有利于我们对正常衰老如何影响学习和记忆过程的理解。