Jara Nery, Cifuentes Manuel, Martínez Fernando, González-Chavarría Iván, Salazar Katterine, Ferrada Lucas, Nualart Francisco
Laboratorio de Neurobiología y Células Madre, NeuroCellT, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción 4030000, Chile.
Department of Cell Biology, Genetics and Physiology, University of Malaga, 29010 Malaga, Spain.
Antioxidants (Basel). 2022 Oct 14;11(10):2030. doi: 10.3390/antiox11102030.
Although scurvy, the severe form of vitamin C deficiency, has been almost eradicated, the prevalence of subclinical vitamin C deficiency is much higher than previously estimated and its impact on human health might not be fully understood. Vitamin C is an essential molecule, especially in the central nervous system where it performs numerous, varied and critical functions, including modulation of neurogenesis and neuronal differentiation. Although it was originally considered to occur only in the embryonic brain, it is now widely accepted that neurogenesis also takes place in the adult brain. The subventricular zone (SVZ) is the neurogenic niche where the largest number of new neurons are born; however, the effect of vitamin C deficiency on neurogenesis in this key region of the adult brain is unknown. Therefore, through BrdU labeling, immunohistochemistry, confocal microscopy and transmission electron microscopy, we analyzed the proliferation and cellular composition of the SVZ and the lateral ventricle (LVE) of adult guinea pigs exposed to a vitamin-C-deficient diet for 14 and 21 days. We found that neuroblasts in the SVZ and LVE were progressively and significantly decreased as the days under vitamin C deficiency elapsed. The neuroblasts in the SVZ and LVE decreased by about 50% in animals with 21 days of deficiency; this was correlated with a reduction in BrdU positive cells in the SVZ and LVE. In addition, the reduction in neuroblasts was not restricted to a particular rostro-caudal area, but was observed throughout the LVE. We also found that vitamin C deficiency altered cellular morphology at the ultrastructural level, especially the cellular and nuclear morphology of ependymal cells of the LVE. Therefore, vitamin C is essential for the maintenance of the SVZ cell populations required for normal activity of the SVZ neurogenic niche in the adult guinea pig brain. Based on our results from the guinea pig brain, we postulate that vitamin C deficiency could also affect neurogenesis in the human brain.
尽管坏血病（维生素C严重缺乏的病症）几乎已被根除，但亚临床维生素C缺乏的患病率比之前估计的要高得多，其对人类健康的影响可能尚未被完全了解。维生素C是一种必需分子，尤其是在中枢神经系统中，它发挥着众多、多样且关键的功能，包括调节神经发生和神经元分化。虽然它最初被认为仅在胚胎大脑中存在，但现在人们普遍接受神经发生也发生在成人大脑中。脑室下区（SVZ）是神经发生的微环境，在此产生的新神经元数量最多；然而，维生素C缺乏对成年大脑这一关键区域神经发生的影响尚不清楚。因此，通过BrdU标记、免疫组织化学、共聚焦显微镜和透射电子显微镜，我们分析了成年豚鼠在摄入维生素C缺乏饮食14天和21天后，其SVZ和侧脑室（LVE）的增殖和细胞组成。我们发现，随着维生素C缺乏天数的增加，SVZ和LVE中的神经母细胞逐渐且显著减少。在缺乏21天的动物中，SVZ和LVE中的神经母细胞减少了约50%；这与SVZ和LVE中BrdU阳性细胞的减少相关。此外，神经母细胞的减少并不局限于特定的头-尾区域，而是在整个LVE中都有观察到。我们还发现，维生素C缺乏在超微结构水平上改变了细胞形态，尤其是LVE室管膜细胞的细胞和细胞核形态。因此，维生素C对于维持成年豚鼠大脑中SVZ神经发生微环境正常活动所需的SVZ细胞群体至关重要。基于我们在豚鼠大脑中的研究结果，我们推测维生素C缺乏也可能影响人类大脑中的神经发生。
