鼻内脂肪蛋白通过促进黑质纹状体通路的神经发生改善帕金森病大鼠模型的运动功能。

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-09-15 DOI:10.1016/j.neuropharm.2025.110687

Seyed Zanyar Athari , Fereshteh Farajdokht , Mohammad Karimipour , Mohammad Reza Alipour , Gisou Mohaddes

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引用次数: 0

摘要

帕金森病（PD）是一种神经退行性疾病，其特征是突触可塑性和神经发生急剧下降，可能是由于α-突触核蛋白沉积异常所致。促进内源性神经发生是阻止细胞死亡和恢复脑功能的潜在策略。AdipoRon （AR）已被证明可促进神经系统疾病中祖细胞的增殖和分化。本研究探讨了鼻内AR对大鼠PD模型黑质纹状体通路神经发生和运动功能的影响。6-羟基多巴胺（6-OHDA）注入左内侧前脑束诱导多巴胺能神经元变性。pd诱导后1周，半帕金森大鼠分别给予左旋多巴（10 mg/kg，灌胃）或AR(0.1、1和10 μg/大鼠，IN) 21天。为了评估成人神经发生，在治疗开始时注射5-溴脱氧尿苷（BrdU） 5天。6-羟多巴胺注射后5周评估运动功能，并处死动物进行分析。测定同侧黑质（SN）中BrdU和NeuN/BrdU阳性细胞的数量。检测纹状体中酪氨酸羟化酶（TH）阳性纤维密度及脑多巴胺神经营养因子（CDNF）、Zif-268、突触素（SYP）蛋白水平。我们的研究结果表明，AR剂量依赖性地恢复了6- ohda损伤大鼠的运动功能，并增加了纹状体CDNF、SYP和Zif-268蛋白的表达。此外，AR 10 μg还能增强纹状体中NeuN+细胞的数量和多巴胺能纤维（TH+末梢）的密度。这些结果表明，AR通过促进PD大鼠黑质纹状体通路的神经发生和突触传递来改善运动症状。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Intranasal AdipoRon improves motor function in a rat model of Parkinson's disease by promoting neurogenesis in the nigrostriatal pathway

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Intranasal AdipoRon improves motor function in a rat model of Parkinson's disease by promoting neurogenesis in the nigrostriatal pathway

Parkinson's disease (PD) is a neurodegenerative disorder characterized by drastically reduced synaptic plasticity and neurogenesis, possibly due to abnormal α-synuclein deposition. Boosting endogenous neurogenesis is a potential strategy for halting cell death and restoring brain function. AdipoRon (AR) has been shown to promote progenitor cell proliferation and differentiation in neurological disorders. This study investigated the effect of intranasal (IN) AR on neurogenesis in the nigrostriatal pathway and motor function in a rat PD model. Dopaminergic neuronal degeneration was induced by administering 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle. One week post-PD induction, hemiparkinsonian rats received either levodopa (10 mg/kg, gavage) or AR (0.1, 1, and 10 μg/rat, IN) for 21 days. To evaluate adult neurogenesis, 5-bromodeoxyuridine (BrdU) was injected for 5 days at the start of treatments. Motor functions were assessed 5 weeks post-6-OHDA injection, and the animals were sacrificed for analysis. The number of BrdU and NeuN/BrdU positive cells in the ipsilateral substantia nigra (SN) was determined. Moreover, the density of tyrosine hydroxylase (TH)-positive fibers and the level of cerebral dopamine neurotrophic factor (CDNF), Zif-268, and synaptophysin (SYP) proteins were examined in the striatum. Our findings indicated that AR dose-dependently restored motor function and increased striatal CDNF, SYP, and Zif-268 protein expression in 6-OHDA-lesioned rats. Besides, AR 10 μg enhanced the number of NeuN + cells in the SN and dopaminergic fiber density (TH + terminals) in the striatum. These findings indicated that AR improved motor symptoms by promoting neurogenesis and synaptic transmission in the nigrostriatal pathway in PD rats.

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).