Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease.

IF 1.8 3区 医学 Q3 UROLOGY & NEPHROLOGY International Neurourology Journal Pub Date : 2022-11-01 DOI:10.5213/inj.2244252.126
Bohye Kim, Poornima D E Weerasinghe-Mudiyanselage, Mary Jasmin Ang, Jeongmin Lee, Sohi Kang, Jong-Choon Kim, Sung-Ho Kim, Joong-Sun Kim, Chaeyong Jung, Taekyun Shin, Changjong Moon
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引用次数: 3

Abstract

Purpose: Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD.

Methods: Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining.

Results: During the 7-8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion.

Conclusion: The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.

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6-羟多巴胺损伤大鼠帕金森病模型海马神经元结构的变化
目的:帕金森病(PD)是一种进行性神经退行性疾病,其中多巴胺能(DAergic)系统被破坏(特别是在黑质纹状体系统),引起运动和非运动症状。海马神经可塑性在PD动物模型中发生改变,导致非运动功能障碍。然而,PD患者海马功能障碍的确切机制尚不清楚。方法:单侧注射成年大鼠纹状体6-羟多巴胺(6-OHDA)。在6- ohda损伤的大鼠中证实了运动和非运动症状以及黑质和纹状体中酪氨酸羟化酶(TH)的表达。采用高尔基染色法分析海马神经元结构。结果:注射后7-8周,6- ohda损伤大鼠出现运动和非运动功能障碍(尤其是焦虑/抑郁样行为)。单侧6-OHDA输注大鼠大脑同侧黑质纹状体通路TH+免疫反应性降低。高尔基染色显示,纹状体6-OHDA灌注显著降低了同侧海马锥体1 (CA1)顶/基区和齿状回(DG)亚区的树突复杂性(即交叉树突数量、树突总长度和分支点)。此外,纹状体注入6-OHDA后,CA1尖/基底区和DG亚区树突棘密度和形态发生了显著改变。然而,纹状体6-OHDA输注后,海马的小胶质细胞和星形胶质细胞分布并未发生改变。结论:本研究为大鼠纹状体6-羟多巴胺输注后海马结构可塑性在后期发生改变提供了解剖学证据,可能是由于对胆能系统的长期抑制,且与神经炎症无关。
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来源期刊
International Neurourology Journal
International Neurourology Journal UROLOGY & NEPHROLOGY-
CiteScore
4.40
自引率
21.70%
发文量
41
审稿时长
4 weeks
期刊介绍: The International Neurourology Journal (Int Neurourol J, INJ) is a quarterly international journal that publishes high-quality research papers that provide the most significant and promising achievements in the fields of clinical neurourology and fundamental science. Specifically, fundamental science includes the most influential research papers from all fields of science and technology, revolutionizing what physicians and researchers practicing the art of neurourology worldwide know. Thus, we welcome valuable basic research articles to introduce cutting-edge translational research of fundamental sciences to clinical neurourology. In the editorials, urologists will present their perspectives on these articles. The original mission statement of the INJ was published on October 12, 1997. INJ provides authors a fast review of their work and makes a decision in an average of three to four weeks of receiving submissions. If accepted, articles are posted online in fully citable form. Supplementary issues will be published interim to quarterlies, as necessary, to fully allow berth to accept and publish relevant articles.
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