Analysis of the Dynamics of Cognitive Impairments and Expression of Caspase Cascade Genes in Preclinical Stages of Parkinsonism Modeled Using α-Synuclein Oligomers

IF 0.9 4区医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL

Bulletin of Experimental Biology and Medicine Pub Date : 2024-09-11 DOI:10.1007/s10517-024-06199-5

M. A. Gruden, V. I. Inokenteva, O. A. Solovieva, N. P. Mikhailova, A. M. Ratmirov, V. V. Sherstnev, Z. I. Storozheva

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Abstract

The behavioral effects of α-synuclein oligomers were studied at various times after its chronic intranasal administration to 75-day-old C57BL/6J mice in comparison with the dynamics of changes in the transcriptional activity of caspases genes (Casp9, Casp8, and Casp3) in the hippocampus, frontal cortex, and cerebellum. The negative effects of α-synuclein oligomers on exploratory activity and short-term memory in the novel object recognition test were most pronounced after 90 days from the end of administration, while after 1 and 270 days, partial compensation of the studied cognitive functions was observed. Analysis of the expression of caspase genes suggests that early compensatory mechanisms are associated with suppression of the effector caspase-3 gene expression along with increased activity of the genes encoding initiator caspases-9 and -8. Late compensation processes are associated with a decrease in the activity of initiator caspases in the frontal cortex and cerebellum.

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使用α-突触核蛋白寡聚体模拟帕金森病临床前阶段认知障碍和Caspase级联基因表达的动态分析

研究了α-突触核蛋白寡聚体对75天大的C57BL/6J小鼠长期鼻内给药后不同时间的行为影响，并与海马、额叶皮层和小脑中Caspases基因（Casp9、Casp8和Casp3）转录活性的动态变化进行了比较。α-突触核蛋白寡聚体对探索活动和新物体识别测试中的短期记忆的负面影响在给药结束90天后最为明显，而在给药1天和270天后，所研究的认知功能得到了部分补偿。对caspase基因表达的分析表明，早期代偿机制与抑制效应caspase-3基因表达以及增加编码启动caspase-9和-8基因的活性有关。晚期代偿过程与额叶皮层和小脑中启动caspase活性的降低有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bulletin of Experimental Biology and Medicine 医学-医学：研究与实验

CiteScore

1.50

自引率

14.30%

发文量

265

审稿时长

2 months

期刊介绍： Bulletin of Experimental Biology and Medicine presents original peer reviewed research papers and brief reports on priority new research results in physiology, biochemistry, biophysics, pharmacology, immunology, microbiology, genetics, oncology, etc. Novel trends in science are covered in new sections of the journal - Biogerontology and Human Ecology - that first appeared in 2005. World scientific interest in stem cells prompted inclusion into Bulletin of Experimental Biology and Medicine a quarterly scientific journal Cell Technologies in Biology and Medicine (a new Russian Academy of Medical Sciences publication since 2005). It publishes only original papers from the leading research institutions on molecular biology of stem and progenitor cells, stem cell as the basis of gene therapy, molecular language of cell-to-cell communication, cytokines, chemokines, growth and other factors, pilot projects on clinical use of stem and progenitor cells. The Russian Volume Year is published in English from April.