Department of Pediatric Neurology, Hubei Maternal and Child Health Hospital, Wuhan, China.
Children's Health Department, Hubei Maternal and Child Health Hospital, Wuhan, China.
Behav Neurol. 2023 May 9;2023:6991826. doi: 10.1155/2023/6991826. eCollection 2023.
Vitamin B6 (VB) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB standard, VB deficiency, or VB supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB treatments. VB deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.
维生素 B6（VB）对自闭症谱系障碍（ASD）具有治疗作用，但具体机制尚不清楚。用 VB 标准、VB 缺乏或 VB 补充饮食处理大鼠母鼠，并对其后代进行相同的处理，监测其体重。采用三腔社交测试和旷场测试评估 VB 对自闭症样行为的影响。通过免疫荧光染色检测大鼠海马神经元中γ-氨基丁酸（GABA）的产生和突触抑制，然后通过高效液相色谱（HPLC）测量 GABA 浓度。通过 Western blot 和末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）测定 VB 在细胞自噬和凋亡中的作用。为了进行挽救实验，通过药物处理 VB 缺乏的后代大鼠来抑制哺乳动物雷帕霉素靶蛋白（mTOR）或激活 GABA。结果，不同 VB 处理的后代体重无明显差异。VB 缺乏会损害社交互动；加剧自我修饰和排便频率；降低 GABA 浓度、VIAAT、GAD67、vGAT 表达和 LC3 II/LC3 I 比值；增加 p62 水平和 p-mTOR/mTOR 比值；并促进细胞凋亡。mTOR 抑制逆转了 VB 缺乏对细胞自噬的影响。GABA 激活或 mTOR 抑制抵消了 VB 缺乏在自闭症样行为和海马 GABA 表达中的作用。总之，VB 缺乏通过调节海马 mTOR 介导的自噬引起大鼠自闭症样行为。
