ERK5 in Learning and Memory

描述（由申请人提供）：学习和记忆缺陷是许多精神障碍的突出特征。了解负责学习和记忆的分子机制是开发治疗精神疾病的治疗方法以改善学习和记忆的关键。最近的研究导致了一个令人兴奋的想法，即成年海马齿状回（DG）中新产生的神经元可能在神经可塑性（包括海马依赖性记忆的形成）中发挥作用。成年神经发生发生在生理条件下的哺乳动物脑（包括成年人脑）的DG中，并且新生成的神经元功能性地整合到DG中。许多因素，包括抑郁症和其他精神疾病可能会对海马成体神经发生产生不利影响。相反，抗抑郁药和运动治疗，一种有效的手段来治疗抑郁症，增强成年DG的神经发生。因此，阐明调节成人海马神经发生的基本分子机制，并产生明确的证据支持成人神经发生在海马依赖性记忆形成中的作用，是心理健康研究的一个关键和及时的问题。虽然许多研究已经评估了成人神经发生在海马依赖性学习和记忆中的作用，但结果并不一致，这使得成人神经发生是否有助于海马依赖性记忆的形成仍然存在很大争议。这项提议将检验ERK 5信号传导介导的成人神经发生在一些但不是所有形式的海马依赖性学习和记忆中起关键作用的假设。 公共卫生相关性：我们提出的研究可能会提供有关调节成人神经发生的信号转导机制的新见解，并可能导致新的见解，以改善精神疾病治疗中的学习和记忆的治疗方法的发展。

DESCRIPTION (provided by applicant): Deficits in learning and memory are prominent features of many mental disorders. Understanding molecular mechanisms responsible for learning and memory are key to the development of therapies to improve learning and memory in the treatment of mental illness. Recent studies lead to the exciting idea that newly generated neurons in the adult dentate gyrus (DG) of the hippocampus may play a role in neural plasticity including hippocampal-dependent memory formation. Adult neurogenesis occurs in the DG of the mammalian brains including adult human brain under physiological conditions and newly generated neurons functionally integrate to the DG. Many factors, including depression and other mental illness may adversely affect hippocampal adult neurogenesis. In contrast, treatment with anti-depressants and exercise, an effective means to treat depression, enhance adult neurogenesis in the DG. Consequently, elucidation of basic molecular mechanisms regulating adult hippocampal neurogenesis and generation of definitive evidence supporting a role for adult neurogenesis in hippocampal-dependent memory formation is a critical and timely issue for mental health research. Although many studies have assessed the role of adult neurogenesis in hippocampal-dependent learning and memory, the results have been inconsistent, making it still highly controversial whether adult neurogenesis contributes to hippocampus-dependent memory formation. This proposal will test the hypothesis that ERK5 signaling-mediated adult neurogenesis plays a critical role in some but not all forms of hippocampal- dependent learning and memory. PUBLIC HEALTH RELEVANCE: Our proposed studies are likely to provide new insights concerning signal transduction mechanisms regulating adult neurogenesis, and may lead to new insights to the development of therapies to improve learning and memory in the treatment of mental illness.