Department of Human Nutrition and Hospitality Management, College of Human Environmental Sciences, The University of Alabama, Tuscaloosa, AL, 35487, USA.
Department of Human Nutrition and Hospitality Management, College of Human Environmental Sciences, The University of Alabama, Tuscaloosa, AL, 35487, USA.
Nutr Res. 2022 May;101:31-42. doi: 10.1016/j.nutres.2022.02.007. Epub 2022 Mar 7.
Alpha-tocotrienol (α-TCT) is a member of the vitamin E family. It has been reported to protect the brain against various pathologies including cerebral ischemia and neurodegeneration. However, it is still unclear if α-TCT exhibits beneficial effects during brain development. We hypothesized that treatment with α-TCT improves intracellular redox homeostasis supporting normal development of neurons. We found that primary hippocampal neurons isolated from rat feti grown in α-TCT-containing media achieved greater levels of neurite complexity compared to ethanol-treated control neurons. Neurons were treated with 1 μM α-TCT for 3 weeks, and media were replaced with fresh α-TCT every week. Treatment with α-TCT increased α-TCT levels (26 pmol/mg protein) in the cells, whereas the control neurons did not contain α-TCT. α-TCT-treated neurons produced adenosine triphosphate (ATP) at a higher rate and increased ATP retention at neurites, supporting formation of neurite branches. Although treatment with α-TCT alone did not change neuronal viability, neurons grown in α-TCT were more resistant to death at maturity. We further found that messenger RNA and protein levels of B-cell lymphoma-extra large (Bcl-xL) are increased by α-TCT treatment without inducing posttranslational cleavage of Bcl-xL. Bcl-xL is known to enhance mitochondrial energy production, which improves neuronal function including neurite outgrowth and neurotransmission. Therefore α-TCT-mediated Bcl-xL upregulation may be the central mechanism of neuroprotection seen in the α-TCT-treated group. In summary, treatment with α-TCT upregulates Bcl-xL and increases ATP levels at neurites. This correlates with increased neurite branching during development and with protection of mature neurons against oxidative stress.
α-生育三烯酚（α-TCT）是维生素 E 家族的一员。据报道，它可以保护大脑免受各种病变的影响，包括脑缺血和神经退行性变。然而，目前尚不清楚 α-TCT 是否在大脑发育过程中表现出有益的作用。我们假设，用 α-TCT 治疗可以改善细胞内氧化还原稳态，从而支持神经元的正常发育。我们发现，与用乙醇处理的对照神经元相比，在含有 α-TCT 的培养基中生长的大鼠胎儿分离的原代海马神经元具有更高水平的神经突复杂性。用 1 μM α-TCT 处理神经元 3 周，每周用新鲜的 α-TCT 替换培养基。用 α-TCT 处理可增加细胞内的 α-TCT 水平（26 pmol/mg 蛋白），而对照神经元则不含 α-TCT。α-TCT 处理的神经元产生三磷酸腺苷（ATP）的速度更快，并且在神经突中保留更多的 ATP，从而支持神经突分支的形成。虽然单独用 α-TCT 处理不会改变神经元的活力，但在 α-TCT 中生长的神经元在成熟时对死亡的抵抗力更强。我们进一步发现，α-TCT 处理可增加 B 细胞淋巴瘤-extra large（Bcl-xL）的信使 RNA 和蛋白水平，而不会诱导 Bcl-xL 的翻译后切割。Bcl-xL 已知可增强线粒体的能量产生，从而改善神经元功能，包括神经突的生长和神经递质的传递。因此，α-TCT 介导的 Bcl-xL 上调可能是 α-TCT 处理组中观察到的神经保护的核心机制。总之，用 α-TCT 处理可上调 Bcl-xL 并增加神经突中的 ATP 水平。这与发育过程中神经突分支增加以及成熟神经元对抗氧化应激的保护作用相关。
