Role and mechanism of nicotinamide adenine dinucleotide in rotenone-induced damage in dopaminergic neurons

GE Wei; LIU Haoyin; DONG Xunhu; YE Wenqi; WANG Xiaogang; YE Feng; ZHAO Yuanpeng; SAI Yan

doi:10.16016/j.2097-0927.202505062

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Role and mechanism of nicotinamide adenine dinucleotide in rotenone-induced damage in dopaminergic neurons

Neuroscience | 更新时间：2025-09-28

- Role and mechanism of nicotinamide adenine dinucleotide in rotenone-induced damage in dopaminergic neurons
- Journal of Army Medical University Vol. 47, Issue 18, Pages: 2163-2173(2025)
- 作者机构：
  
  陆军军医大学（第三军医大学）军事预防医学系防化医学教研室，重庆
- 作者简介：
- 基金信息：
  
  Supported the General Program of National Natural Science Foundation of China(81973090)
- DOI：10.16016/j.2097-0927.202505062
  CLC： R742.5;R977.6;R996.2
- Received：26 May 2025，
  
  Revised：2025-08-28，
  
  Accepted：02 September 2025，
  
  Published：30 September 2025
- 稿件说明：
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葛维，刘浩银，董训虎，等.烟酰胺腺嘌呤二核苷酸在鱼藤酮诱导的多巴胺神经元损伤中的作用和机制研究［J］.陆军军医大学学报，2025，47（18）：2163-2173.DOI：10.16016/j.2097-0927.202505062.

GE WEI，LIU HAOYING，DONG XUNHU，et al.Role and mechanism of nicotinamide adenine dinucleotide in rotenone-induced damage in dopaminergic neurons［J］.J Army Med Univ，2025，47（18）：2163-2173.DOI：10.16016/j.2097-0927.202505062.
葛维，刘浩银，董训虎，等.烟酰胺腺嘌呤二核苷酸在鱼藤酮诱导的多巴胺神经元损伤中的作用和机制研究［J］.陆军军医大学学报，2025，47（18）：2163-2173.DOI：10.16016/j.2097-0927.202505062. DOI：

GE WEI，LIU HAOYING，DONG XUNHU，et al.Role and mechanism of nicotinamide adenine dinucleotide in rotenone-induced damage in dopaminergic neurons［J］.J Army Med Univ，2025，47（18）：2163-2173.DOI：10.16016/j.2097-0927.202505062. DOI：

摘要

目的

探讨鱼藤酮暴露对大鼠中脑纹状体多巴胺神经元烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide，NAD

）代谢稳态的作用，以及外源性NAD

干预对鱼藤酮诱导的多巴胺神经元细胞损伤的影响。

方法

将8周龄雄性SD大鼠（200~250 g）按随机数字表法分为（

=10）：对照组、鱼藤酮暴露组、NAD

干预组、NAD

组。用鱼藤酮暴露组建立染毒模型，NAD

干预组在染毒同时给予NAD

（250 mg/kg），NAD

组仅给予NAD

，对照组不干预。造模后通过旷场实验评估行为学变化，处死后收集血清及中脑纹状体组织。HE染色观察纹状体多巴胺神经元形态；NAD

/NADH试剂盒检测组织中NAD

水平；Western blot检测酪氨酸羟化酶（tyrosine hydroxylase，TH）、烟酰胺磷酸核糖转移酶（nicotinamide phosphoribosyltransferase，NAMPT）、烟酰胺单核苷酸腺苷酸转移酶（nico

tinamide mononucleotide adenylyltransferase，NMNAT）、溶质载体家族25成员A51（solute carrier family 25 member 51，SLC25A51）的含量；ELISA检测纹状体组织中多巴胺的含量；免疫组织化学染色观察各组纹状体组织中TH蛋白的分布和含量。

结果

鱼藤酮暴露影响大鼠的生命体征和运动能力，纹状体组织神经元细胞排列紊乱、萎缩变形；多巴胺合成限速酶TH蛋白的含量显著下降约29%（

0.01），多巴胺含量下降约42%；NAD

含量降低约50%（

0.01），NADH/NAD

比值提升（

0.01）；NAD

合成相关酶NAMPT显著下降约26%（

0.05）；NMNAT1-3及NAD

线粒体转运蛋白SLC25A51的含量分别下降约21%、38%、43%、21%（

0.01）。外源性NAD

干预后，显著改善鱼藤酮暴露大鼠的运动功能和中脑纹状体组织多巴胺神经元形态；纹状体组织中TH蛋白显著恢复约12.8%（

0.05）、多巴胺水平恢复约20.9%（

0.05）。

结论

鱼藤酮通过抑制大鼠中脑纹状体组织中NAD

合成、转运通路，破坏多巴胺神经元组织的NAD

稳态，而外源性NAD

干预可有效改善鱼藤酮暴露诱导的多巴胺神经元损伤。

Abstract

Objective

To explore the effect of rotenone exposure on the metabolic homeostasis of nicotinamide adenine dinucleotide (NAD

) in dopaminergic neurons of the rat mid-brain striatum

and investigate the effect of exogenous NAD

intervention on the cellular damage response of dopaminergic neurons induced by rotenone.

Methods

Male SD rats (8 weeks old

200~250 g) were divided into a control group using a table of random numbers

a rotenone exposure group

an NAD

-intervention group

and an NAD

group. An intoxication model was established in the rotenone exposure group. NAD

(250 mg/kg) was administered simultaneously with rotenone exposure in the NAD

-intervention group. The NAD

group was only given NAD

while the control group received no intervention. After modeling

open field test was performed to evaluate behavioral changes. After scarification

serum samples and mid-brain striatal tissues were collected. HE staining was used to observe the morphology of dop

aminergic neurons in the striatum. The NAD

content in the tissues was detected with NAD

/NADH kit. Western blotting was employed to determine the contents of tyrosine hydroxylase (TH)

nicotinamide phosphoribosyltransferase (NAMPT)

nicotinamide mononucleotide adenylyltransferase (NMNAT)

and solute carrier family 25 member A51 (SLC25A51). ELISA was utilized to measure the content of dopamine in the striatal tissues. Immunohistochemical staining was applied to observe the distribution and contents of TH proteins in the striatal tissues of each group.

Results

Rotenone exposure significantly affected the vital signs and motor abilities of rats

induced disorderly-arranged

atrophy and deformed neurons in the striatal tissue

decreased the content of TH

rate-limiting enzyme for dopamine synthesis

by approximately 29% (

0.01)

the content of dopamine by about 42%

and that of NAD

by almost 50% (

0.01)

while increased the NADH/NAD

ratio (

0.01). After exposure

the content of NAMPT

an enzyme related to NAD

synthesis

was decreased by 26% (

0.05)

the contents of NMNAT1-3 and SLC25A51

mitochondrial transporters of NAD

by approximately 21%

38%

43%

and 21%

respectively (

0.01). Exogenous NAD

intervention improved the motor function of exposure rats and the morphology of dopaminergic neurons in the mid-brain striatal tissue

and restored the content of TH in the striatal tissue significantly by 12.8% (

0.05)

and the content of dopamine by 20.9% (

0.05).

Conclusion

Rotenone disrupts the NAD

homeostasis in dopaminergic neurons by inhibiting the NAD

synthesis and transport pathways in the mid-brain striatal tissues

while exogenous NAD

intervention can effectively alleviate the dopaminergic ne

uron damage induced by rotenone exposure.

关键词

Keywords

references

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