Department of Developmental and Behavioral Pediatrics, Children's Hospital, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
School of Public Health, Jilin University, Changchun, Jilin Province, China.
Eur Child Adolesc Psychiatry. 2024 Sep;33(9):3189-3201. doi: 10.1007/s00787-024-02376-z. Epub 2024 Feb 23.
Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.
患有慢性抽动障碍（CTD）的儿童，包括妥瑞氏综合征（TS），其血清 25-羟维生素 D [25(OH)D]明显降低。虽然维生素 D3 补充（VDS）可能会减轻这些儿童的抽动症状，但它的作用机制尚不清楚。本研究旨在探讨维生素 D 缺乏（VDD）和 VDS 对 TS 模型行为的影响及其机制。40 只 5 周龄雄性 Sprague-Dawley 大鼠随机分为（每组 10 只）：对照组、TS 模型组、TS 模型加 VDD 组（TS+VDD）或 TS 模型加 VDS 组（TS+VDS；两次肌肉注射 20000 IU/200 g）。VDD 模型通过饮食诱导（0 IU 维生素 D/kg）；TS 模型通过亚氨基二丙腈（IDPN）诱导。所有组均进行行为、血清和纹状体 25(OH)D 和多巴胺（DA）、维生素 D 受体（VDR）、胶质细胞源性神经营养因子（GDNF）、原癌基因酪氨酸蛋白激酶受体 Ret（c-Ret）以及纹状体中 DA D1（DRD1）和 D2（DRD2）受体基因的 mRNA 表达。TS+VDD 组在整个实验过程中行为活动评分更高，21 天时总行为评分也更高。相反，21 天时 TS+VDS 的刻板行为评分和总分均低于 TS 模型组。TS+VDD 的血清 25(OH)D ＜20ng/mL，低于对照组。TS 的纹状体 DA 低于对照组。与 TS 模型组相比，TS+VDD 的纹状体 DA 更低，而 TS+VDS 的纹状体 DA 则高于 TS 模型组。此外，与 TS 模型组相比，TS 模型组 VDR、GDNF 和 c-Ret 基因的 mRNA 表达降低，VDD 组 GDNF 表达降低更为明显，而 VDS 组 GDNF 和 c-Ret 表达升高。VDD 加重，VDS 改善 IDPN 诱导模型中的抽动样行为。VDS 可能通过 VDR 上调 GDNF/c-Ret 信号活性，逆转纹状体 DA 减少并缓解抽动样行为。
