aCenter for Neuroscience bDepartment of Biological Sciences cClinical Laboratory Science, University of Massachusetts Lowell, Lowell, Massachusetts, USA.
Curr Opin Psychiatry. 2014 Mar;27(2):138-42. doi: 10.1097/YCO.0000000000000046.
Nutrition exerts a pervasive impact on normal and pathological conditions of the nervous system. One critical pathway is the methionine cycle, in which folate and B12 convert homocysteine to methionine, which is in turn converted to S-adenosyl methionine (SAM; the major methyl donor). As a consequence of methylation, however, SAM is converted to the neurotoxin homocysteine and must be excreted or drawn back into the methionine cycle, which requires additional folate and B12. Dietary or genetic folate deficiency impairs this cycle, leading to developmental disorders, including those of the nervous system.
Folate and SAM exert profound epigenetic effects via DNA and histone methylation. Maternal supplementation during pregnancy has fostered an increase in individuals harboring genetic polymorphisms that compromise folate usage. Such individuals harbor a lifetime requirement for additional dietary folate, often not met beyond peri/postnatal periods. Herein, we consider the potential link of failure to meet this additional requirement to early and age-related cognitive compromise.
Compromises in the methionine cycle can manifest as a spectrum of disorders throughout life. These considerations underscore how prenatal nutritional supplementation can alleviate developmental disorders by inadvertently establishing latent conditions that, in the absence of continued supplementation, may lead to age-related cognitive decline.
营养对神经系统的正常和病理状况都有广泛的影响。其中一个关键途径是蛋氨酸循环，在这个循环中，叶酸和 B12 将同型半胱氨酸转化为蛋氨酸，蛋氨酸又转化为 S-腺苷甲硫氨酸（SAM；主要的甲基供体）。然而，由于甲基化，SAM 转化为神经毒素同型半胱氨酸，必须被排出或重新进入蛋氨酸循环，这需要额外的叶酸和 B12。饮食或遗传叶酸缺乏会损害这个循环，导致发育障碍，包括神经系统的发育障碍。
叶酸和 SAM 通过 DNA 和组蛋白甲基化产生深远的表观遗传效应。妊娠期间的母体补充促进了携带影响叶酸利用的遗传多态性的个体数量增加。这些个体一生都需要额外的膳食叶酸，而这种需求往往在围产期之后无法得到满足。在此，我们考虑未能满足这一额外需求与早期和与年龄相关的认知能力下降之间的潜在联系。
蛋氨酸循环的缺陷可以表现为一生中一系列的疾病。这些考虑强调了产前营养补充如何通过无意中建立潜在的条件来减轻发育障碍，而在没有持续补充的情况下，这些条件可能会导致与年龄相关的认知能力下降。
