Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
Department of Basic and Clinical Neuroscience, King's College London, London, UK.
Neurobiol Aging. 2020 Jan;85:140-144. doi: 10.1016/j.neurobiolaging.2019.10.001. Epub 2019 Oct 14.
Age-associated cognitive impairments affect an individual's quality of life and are a growing problem in society. Therefore, therapeutic strategies to treat age-related cognitive decline are needed to enhance the quality of life among the elderly. Activation of the Nr4a family of transcription factors has been closely linked to memory formation and dysregulation of these transcription factors is thought to be associated with age-related cognitive decline. Previously, we have shown that Nr4a transcription can be activated by synthetic bisindole-derived compounds (C-DIM). C-DIM compounds enhance synaptic plasticity and long-term contextual fear memory in young healthy mice. In this study, we show that activation of Nr4a2 by 1,1-bis(3'-Indolyl)-1-(p-chlorophenyl) methane (C-DIM12), enhances long-term spatial memory in young mice and rescues memory deficits in aged mice. These findings suggest that C-DIM activators of Nr4a transcription may be suitable to prevent memory deficits associated with aging.
年龄相关的认知障碍影响个体的生活质量，是社会面临的一个日益严重的问题。因此，需要有治疗与年龄相关的认知衰退的策略来提高老年人的生活质量。Nr4a 转录因子家族的激活与记忆形成密切相关，这些转录因子的失调被认为与年龄相关的认知衰退有关。以前，我们已经表明，合成双吲哚衍生化合物（C-DIM）可以激活 Nr4a 转录。C-DIM 化合物增强年轻健康小鼠的突触可塑性和长期情景性恐惧记忆。在这项研究中，我们表明，1,1-双（3'-吲哚基）-1-（对氯苯基）甲烷（C-DIM12）激活 Nr4a2 可增强年轻小鼠的长期空间记忆，并挽救老年小鼠的记忆缺陷。这些发现表明，Nr4a 转录的 C-DIM 激活剂可能适合预防与衰老相关的记忆缺陷。
