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米诺环素对雄性大鼠β-淀粉样蛋白诱导的记忆和学习缺陷的影响:行为学、生物化学和组织学研究。

The effect of minocycline on beta-amyloid-induced memory and learning deficit in male rats: A behavioral, biochemical, and histological study.

机构信息

Student Research Committee, Kermanshah University of Medical Science, Kermanshah, Iran.

Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

J Chem Neuroanat. 2022 Nov;125:102158. doi: 10.1016/j.jchemneu.2022.102158. Epub 2022 Sep 6.

DOI:10.1016/j.jchemneu.2022.102158
PMID:36084891
Abstract

OBJECTIVES

Minocycline hydrochloride is a semi-synthetic, second-generation tetracycline with neuroprotective, neurorestorative, anti-amyloidogenic, anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the potential protective effects of minocycline against beta-amyloid (Aβ)-induced Alzheimer's disease (AD), recognition memory decline, and the possible involved anti-apoptotic mechanisms.

METHODS

The rats were treated with minocycline (50 and 100 mg/kg/day; P.O.) after AD induction for 30 days. Behavioral functions were assessed by employing standard behavioral tests, including novel object recognition (NOR) and passive avoidance learning (PAL) tasks. Then, total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in blood serum using ELISA kits. Apoptosis and the number of Aβ plaques were examined by the TUNEL and Congo red staining, respectively.

RESULTS

Treatment of Aβ rats with minocycline improved memory deficit in the PAL task and a decline in recognition memory in the NOR test. Minocycline at 50 and 100 mg/kg significantly reduced the TOS levels and increased the TAC levels (P < 0.0001). Also, minocycline at 50 and 100 mg/kg reduced the apoptotic index in the hippocampus of Aβ rats. After Congo red staining, the minocycline group showed improved cell morphology and markedly fewer Aβ plaques.

CONCLUSIONS

Minocycline reduced memory and learning deficit in behavioral experiments after Aβ injection, which may be due to its anti-inflammatory and anti-apoptotic effects.

摘要

目的

盐酸米诺环素是一种半合成的第二代四环素,具有神经保护、神经修复、抗淀粉样变性、抗炎、抗氧化和抗细胞凋亡作用。本研究旨在探讨米诺环素对β-淀粉样蛋白(Aβ)诱导的阿尔茨海默病(AD)、识别记忆减退的潜在保护作用,以及可能涉及的抗细胞凋亡机制。

方法

AD 诱导后 30 天,用米诺环素(50 和 100mg/kg/天;P.O.)治疗大鼠。采用标准行为测试,包括新物体识别(NOR)和被动回避学习(PAL)任务评估行为功能。然后,使用 ELISA 试剂盒测定血清中的总抗氧化能力(TAC)和总氧化状态(TOS)。通过 TUNEL 和刚果红染色分别检测细胞凋亡和 Aβ斑块数量。

结果

用米诺环素治疗 Aβ 大鼠可改善 PAL 任务中的记忆缺陷和 NOR 测试中的识别记忆下降。米诺环素 50 和 100mg/kg 可显著降低 TOS 水平,增加 TAC 水平(P<0.0001)。此外,米诺环素 50 和 100mg/kg 可降低 Aβ 大鼠海马中的细胞凋亡指数。刚果红染色后,米诺环素组显示细胞形态改善,Aβ 斑块明显减少。

结论

米诺环素降低了 Aβ 注射后行为实验中的记忆和学习缺陷,这可能与其抗炎和抗细胞凋亡作用有关。

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