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Morphofunctional Changes in the Brain Nervous Tissue of 5xFAD Transgenic Mice

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Abstract

In the present study, in modeling the pathogenesis of Alzheimer’s disease in 5xFAD transgenic mice, a comparative analysis of structural and ultrastructural changes in the nervous tissue of the olfactory bulbs, hippocampus, and entorhinal cortex was performed; in addition, the distribution of the main amyloid-degrading neuropeptidase, neprilysin (NEP), relative to wild-type mice was examined. The investigation of the structure of the nervous tissue showed that the death of brain neurons increased in transgenic animals characterized by increased production of the amyloid peptide Aβ. As a result, connections between neurons were interrupted and the neural network become disrupted. Our electron-microscopy examination revealed a reduced density of synaptic contacts and dendritic spines, local lesions of the nervous tissue, and the appearance of autophagolysosomes in the neuropil tissue of these structures in 5xFAD mice. Signs indicating increased neurodegenerative processes compared with wild-type mice were visible. In 5xFAD mice, the distribution of amyloid-degrading peptidase NEP in the entorhinal cortex and hippocampus was altered, and there was a decreased intensity of its staining in the entorhinal cortex. In transgenic mice aged 6 months, memory impairment was observed in the recognition test of new objects relative to wild-type mice.

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ACKNOWLEDGMENTS

The authors express their deep gratitude to the Center for Collective Use of Scientific Equipment for Physiological, Biochemical, and Molecular Biological Research of the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.

Funding

This work was supported by the Russian Foundation for Basic Research (project no. 19-015-00232) and partly by a state order to the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences (no. AAAA-A18-118012290373-7).

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    N. L. Tumanova, D. S. Vasiliev, N. M. Dubrovskaya & N. N. Nalivaeva

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  1. N. L. Tumanova
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  2. D. S. Vasiliev
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  3. N. M. Dubrovskaya
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  4. N. N. Nalivaeva
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Contributions

N.L. Tumanova, morphological studies, article writing; D.S. Vasiliev, morphological and immunohistochemical assay, statistical data processing; N.M. Dubrovskaya, behavioral experiments and statistical processing of data; N.N. Nalivaeva, data analysis, writing and editing the text of the article, general management of the work. The text and images are approved by all coauthors.

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Correspondence to D. S. Vasiliev.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement on the welfare of animals. Experiments with animals were carried out in accordance with the approved protocol for the use of laboratory animals of the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, on the basis of European Communities Council Directive no. 86/609 for the Care of Laboratory Animals.

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Translated by I. Fridlyanskaya

Abbreviations: APP—β-amyloid peptide precursor, AD—Alzheimer’s disease, Aβ—β-amyloid peptide, PS1—presenilin 1, EPR—endoplasmic reticulum.

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Tumanova, N.L., Vasiliev, D.S., Dubrovskaya, N.M. et al. Morphofunctional Changes in the Brain Nervous Tissue of 5xFAD Transgenic Mice. Cell Tiss. Biol. 16, 380–391 (2022). https://doi.org/10.1134/S1990519X22040095

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