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Developmental Profile of Brain Neprilysin Expression Correlates with Olfactory Behaviour of Rats

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Abstract

A neuropeptidase, neprilysin (NEP), is a major amyloid (Aβ)-degrading enzyme involved in the pathogenesis of Alzheimer’s disease (AD). The olfactory system is affected early in AD with characteristic Aβ accumulation, but data on the dynamics of NEP expression in the olfactory system are absent. Our study demonstrates that NEP mRNA expression in rat olfactory bulbs (OB), entorhinal cortex (ECx), hippocampus (Hip), parietal cortex (PCx) and striatum (Str) increases during the first postnatal month being the highest in the OB and Str. By 3 months, NEP mRNA levels sharply decrease in the ECx, Hip and PCx and by 9 months in the OB, but not in the Str, which correlates with declining olfaction in aged rats tested in the food search paradigm. One-month-old rats subjected to prenatal hypoxia on E14 had lower NEP mRNA levels in the ECx, Hip and PCx (but not in the OB and Str) compared with the control offspring and demonstrated impaired olfaction in the odour preference and food search paradigms. Administration to these rats of a histone deacetylase inhibitor, sodium valproate, restored NEP expression in the ECx, Hip and PCx and improved olfaction. Our data support NEP involvement in olfactory function.

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Acknowledgements

The authors are grateful to Dr. Olga S Alekseeva for her assistance in performing PH experiments. Molecular biology experiments were performed using the facilities of the Research Resource Centre for physiological, biochemical, and molecular-biological research of the Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences.

Funding

The work was supported by the Russian Foundation for Basic Research, grant 19–015-00232, and Russian Federation state budget (assignment AAAA-A18-118012290373–7).

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Contributions

All authors have been participating in the design of the study and discussion of the results. Dr DS Vasilev performed the tissue extraction, rt-PCR and statistical analysis of the data. Dr. NM Dubrovskaya performed the animal and behavioural experiments and statistical analysis of the data. Dr. NN Nalivaeva built the concept of the study and wrote the manuscript. Dr. IA Zhuravin supervised the performance of the whole study and its preparation for publication.

Corresponding author

Correspondence to Natalia N. Nalivaeva.

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Competing Interests

The authors declare that they have no competing interests.

Ethics Approval

All procedures were carried out in accordance with the international guidelines for work with experimental animals and 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.

Consent for Publication

All the authors read and agreed to publish this paper. Dr. Igor A Zhuravin before his untimely death has seen all the results and the completed version of the manuscript and agreed with it. The submitted work is original and has not been published elsewhere and is not under consideration in any other journal.

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The authors with great sadness report the death of Dr Igor A Zhuravin during the final stages of this manuscript preparation.

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Vasilev, D.S., Dubrovskaya, N.M., Zhuravin, I.A. et al. Developmental Profile of Brain Neprilysin Expression Correlates with Olfactory Behaviour of Rats. J Mol Neurosci 71, 1772–1785 (2021). https://doi.org/10.1007/s12031-020-01786-3

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  • DOI: https://doi.org/10.1007/s12031-020-01786-3

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