Bekdash Rola Aldana
Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.
Adv Neurobiol. 2016;12:381-99. doi: 10.1007/978-3-319-28383-8_21.
Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and may alter brain function. Besides its role in methyl group metabolism, choline also has pivotal functions, including the maintenance of structural integrity of membranes and modulation of cholinergic neurotransmission, functions that are often dysregulated in some neurodegenerative disorders. Emerging evidence suggests that environmental factors, including lifestyle or diet, sometimes cause epigenetic changes in the expression of neuronal genes resulting in long-term changes in brain function. Recently, choline has been implicated as an epigenetic modifier of the genome that may alter gene methylation, expression, and cellular function. Abnormal level of choline during fetal or early postnatal life has been shown to alter memory functions during adulthood. It may also contribute to the etiology of stress-related disorders and age-related decline in memory later in life. Conversely, rodent studies suggested that perinatal choline supplementation enhances performance in memory-related tasks during adulthood. In this chapter, we will focus on the impact of choline-gene interaction on brain function in early life and during adulthood. In particular, we will emphasize the potential role of choline as a neuroprotectant that may mitigate some of the adverse effects of neurodegenerative disorders and protect mental health across the lifespan.
胆碱是一种必需营养素,是大脑正常发育所必需的。它通过其代谢产物甜菜碱参与S-腺苷甲硫氨酸的合成,S-腺苷甲硫氨酸是组蛋白和DNA甲基化的主要甲基供体,这两种表观遗传机制调节基因表达并可能改变脑功能。除了在甲基代谢中的作用外,胆碱还具有关键功能,包括维持膜的结构完整性和调节胆碱能神经传递,这些功能在某些神经退行性疾病中常常失调。新出现的证据表明,包括生活方式或饮食在内的环境因素有时会导致神经元基因表达的表观遗传变化,从而导致脑功能的长期改变。最近,胆碱被认为是基因组的一种表观遗传修饰剂,可能会改变基因甲基化、表达和细胞功能。胎儿期或出生后早期胆碱水平异常已被证明会改变成年后的记忆功能。它也可能导致应激相关疾病的病因以及晚年与年龄相关的记忆力下降。相反,啮齿动物研究表明,围产期补充胆碱可提高成年后与记忆相关任务的表现。在本章中,我们将重点关注胆碱-基因相互作用对生命早期和成年期脑功能的影响。特别是,我们将强调胆碱作为一种神经保护剂的潜在作用,它可能减轻一些神经退行性疾病的不良影响,并在整个生命周期中保护心理健康。