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Neurodegenerative Changes in the Structural and Ultrastructural Organization in the Pyriform Cortex of 5xFAD Transgenic Mice

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Abstract

Analysis of pathological changes in the structural and functional organization of the pyriform cortex in mice of the 5xFAD line, which models the pathogenesis of Alzheimer’s disease, showed that at the age of 7 months there is an increased aggregation of β-amyloid peptide, neuronal death, disintegration of myelin sheaths of nerve fibers, agglutination of synaptic vesicles in synaptic endings and the appearance of a large number of autophagolysosomes in the bodies and processes of neurons. Also, in the pyriform cortex of such animals, foci of gliosis and an almost threefold increase in the content of the glial marker protein GFAP compared with wild type animals were found. All these changes were more pronounced than in the entorhinal cortex of 5xFAD mice that we had previously studied. Between the pyriform and entorhinal regions, a difference in the distribution of the amyloid-degrading metallopeptidase neprilysin (NEP) was also revealed. In the pyriform cortex, this enzyme is found mainly in the intercellular space, whereas in the entorhinal cortex, in the cell bodies. Moreover, in the entorhinal cortex of 5xFAD mice, the number of NEP-positive cells was 60% lower than in wild-type mice. 5xFAD mice also showed a significant deterioration in olfactory function, which was expressed in an almost twofold decrease in the effectiveness of the search for food by smell compared to wild-type mice. These findings suggest significant pathological changes in the pyriform and entorhinal cortex in 5xFAD mice caused by amyloid accumulation, which may cause a deterioration in their sense of smell, and similarly might cause impaired olfactory function in the development of Alzheimer’s disease.

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Abbreviations

AD:

Alzheimer’s disease

Аβ:

β-amyloid peptide

GFAP:

glial fibrillary acidic protein

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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 (CCU) of the IEPhB RAS.

Funding

The work was carried out with the financial support of the State Budget Assignment of I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (No 075-00408-21-00).

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Authors and Affiliations

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

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

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Contributions

NLN: morphological studies, writing an article; DSV: morphological and immunohistochemical studies, statistical data processing, article editing; NMD: behavioral experiments and statistical data processing; NNN: data analysis, writing and editing the text of the article, general management of the work. The text and graphic images of the article are approved by all co-authors.

Corresponding author

Correspondence to D. S. Vasilev.

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COMPLIANCE WITH Ethical staNDARDS

All experiments were carried out in compliance with the international guidelines for work with experimental animals, the guidelines of the Russian Academy of Sciences (RAS) and approved by the Scientific Ethical Council of the Institute of Evolutionary Physiology and Biochemistry RAS.

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Authors declare no conflict of interests.

Additional information

Translated by N. Nalivaeva

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 8, pp. 997–1014https://doi.org/10.31857/S086981392208009X.

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Tumanova, N.L., Vasilev, D.S., Dubrovskaya, N.M. et al. Neurodegenerative Changes in the Structural and Ultrastructural Organization in the Pyriform Cortex of 5xFAD Transgenic Mice. J Evol Biochem Phys 58, 1225–1239 (2022). https://doi.org/10.1134/S0022093022040251

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