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氯化铝诱导神经退行性变的成年和老年Wistar大鼠脑和外周血的形态功能变化

Morphofunctional Changes in Brain and Peripheral Blood in Adult and Aged Wistar Rats with AlCl-Induced Neurodegeneration.

作者信息

Sentyabreva Alexandra Vladislavovna, Miroshnichenko Ekaterina Alexandrovna, Melnikova Ekaterina Andreevna, Tsvetkov Ivan Sergeevich, Kosyreva Anna Mikhailovna

机构信息

Avtsyn Research Institute of Human Morphology of "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia.

Research Institute of Molecular and Cellular Medicine, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia.

出版信息

Biomedicines. 2023 Aug 22;11(9):2336. doi: 10.3390/biomedicines11092336.

Abstract

BACKGROUND

the general lifespan has been prolonged greatly during the past century, and the incidence of age-associated diseases, including neurodegenerative ones, has increased as well. However, modelling of age-related pathologies is mostly conducted on adult rodents. We studied morphofunctional changes in the brain and peripheral blood of adult Wistar rats in comparison with old Wistar rats to determine age-related physiological changes and differences in adaptive reactions to AlCl exposure.

METHODS

the work was performed on adult and old male Wistar rats. The animals consumed a 100 mg/kg solution of AlCl each day for 60 days. Morphological changes of neurons and microglia, mRNA expression levels of pro-inflammatory and anti-inflammatory cytokines, microglia activation markers, amyloid-related proteins, and hallmarks of cellular senescence, monocyte, and lymphocyte subpopulations in the peripheral blood were examined.

RESULTS

old rats showed increasing hyperchromic neurons in the hippocampus; activation of microglia; upregulation of pro-inflammatory cytokines and cellular senescence markers; downregulation of anti-inflammatory cytokines; and and a decrease in B-cells and monocyte in peripheral blood.

CONCLUSION

compared to young animals, aged rats respond to aluminum exposure with a severe decline of most cells' function and irreversible neuronal loss. Regarding all reported data, neurodegeneration modelling and investigating of factors capable of accelerating or preventing it should be performed in experimental work on aged animals.

摘要

背景

在过去的一个世纪里,人类的总体寿命大幅延长,包括神经退行性疾病在内的与年龄相关疾病的发病率也有所上升。然而,与年龄相关的病理学模型大多是在成年啮齿动物身上建立的。我们研究了成年Wistar大鼠与老年Wistar大鼠大脑和外周血中的形态功能变化,以确定与年龄相关的生理变化以及对氯化铝暴露的适应性反应差异。

方法

对成年和老年雄性Wistar大鼠进行实验。动物每天饮用100mg/kg的氯化铝溶液,持续60天。检测神经元和小胶质细胞的形态变化、促炎和抗炎细胞因子的mRNA表达水平、小胶质细胞活化标志物、淀粉样相关蛋白以及细胞衰老标志物、外周血中的单核细胞和淋巴细胞亚群。

结果

老年大鼠海马区出现核仁染色质增多的神经元数量增加;小胶质细胞活化;促炎细胞因子和细胞衰老标志物上调;抗炎细胞因子下调;外周血中B细胞和单核细胞减少。

结论

与年轻动物相比,老年大鼠对铝暴露的反应是大多数细胞功能严重下降和不可逆的神经元损失。基于所有已报道的数据,在老年动物的实验研究中应进行神经退行性变建模以及对能够加速或预防神经退行性变的因素进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34cb/10526012/2d32eb9a3bcf/biomedicines-11-02336-g001.jpg

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