Decreased brain levels of vitamin B12 in aging, autism and schizophrenia

Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched co...诸多研究表明，依赖维生素B12与叶酸的甲硫氨酸合酶（methionine synthase, MS）在大脑发育与功能中发挥关键作用，但此前尚无研究针对全生命周期内大脑的维生素B12水平展开探究。维生素B12（钴胺素, Cbl）存在多种形式，包括甲基钴胺素（methylcobalamin, MeCbl）与腺苷钴胺素（adenosylcobalamin, AdoCbl），二者分别作为甲硫氨酸合酶与甲基丙二酰辅酶A变位酶的辅因子。本研究检测了43名对照受试者的死后人类前额叶皮层中5种钴胺素形式的水平，受试者覆盖孕19周至80岁的人群，同时纳入12名自闭症受试者与9名精神分裂症受试者。老年对照组受试者（年龄＞60岁）的总钴胺素水平显著降低，这主要源于甲基钴胺素水平出现10倍以上的年龄依赖性下降。胎儿脑组织样本中的无活性氰钴胺素（cyanocobalamin, CNCbl）水平显著升高。自闭症与精神分裂症受试者体内的甲基钴胺素与腺苷钴胺素水平均较同年龄匹配的对照组低3倍以上……