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Patterns of Expression of the Key Genes of the BDNF System and Serotonin Receptors in the Brain of OXYS Rats in the Development of the Signs of Alzheimer’s Disease

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Abstract

In spite of numerous studies, pathogenesis of the sporadic (not inherited) form of Alzheimer’s disease (AD) still remains largely unclear; nevertheless, there is general consensus as regards the complex involvement of neurotrophic factors and neurotransmitters in the mechanisms of this disease. In light of recent data on the physical interaction between serotonin (5-HT) receptors and receptors of the brain-derived neurotrophic factor (BDNF), the reciprocal modulation between 5-HT and BDNF systems is of particular interest, inter alia, in the context of AD development. The OXYS lineage of prematurely aging rats is a unique model of sporadic AD. Previously, it has been reported on the changed neurotrophin balance in the brain of these animals; however, the changes in the expression of BDNF and its receptors in the dynamics of development of AD symptoms has been studied insufficiently. Even less is known about the patterns of expression of 5-HT receptors in OXYS rat brain. In the present work, we have compared the expression of BDNF and its receptors, TrkB and p75NTR, as well as serotonin 5-НТ1А, 5-НТ2А, 5-НТ4 and 5-НТ7 receptors in the brain of OXYS and Wistar rats aged 20 days, 3.5 and 18 months. The frontal cortex of 20-day-old OXYS rats demonstrated a significant increase in the mRNA level of the Bdnf, Htr2a and Htr7 genes and, at the same time, a decrease in the ratio of phosphorylated and nonphosphorylated forms of the TrkB receptor. In the hippocampus of 20-day-old OXYS rats, the mRNA levels of the Bdnf, Htr1a, Htr2a and Htr4 genes are also elevated. A substantially higher mRNA level of the above genes for 5-HT receptors was observed in the hippocampus of OXYS rats also at the age of 3.5 months, in the period of manifestation of the first AD symptoms. The nature of change in gene expression patterns indicates the potential involvement of 5-HT receptors in suppression of the TrkB receptor function in the early period of postnatal development of OXYS rats, which may be one of the mechanisms, through which 5-HT receptors are involved in the development of pathological process in the period of manifestation of AD symptoms in OXYS rats.

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ACKNOWLEDGMENTS

Animal management was supported by the funds of Budget Project no. FWNR-2022-0023.

Funding

The work was supported by the Russian Science Foundation (project no. 22-15-00011).

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    M. Alsallum, Ya. P. Kaminskaya, A. S. Tsybko, N. G. Kolosova & V. S. Naumenko

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  1. M. Alsallum
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  2. Ya. P. Kaminskaya
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  3. A. S. Tsybko
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  4. N. G. Kolosova
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Correspondence to A. S. Tsybko.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Animal-related experiments were conducted in accordance with the NIH Guidelines for the care and use of laboratory animals (http://oacu.od.nih.gov/regs/index.htm). Animal protocols were approved by the Ethics Committee of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences.

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Translated by E. Makeeva

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Abbreviations: 5-HT, serotonin; 5-HT1А receptor, serotonin subtype 1A receptor; 5-HT2А receptor, serotonin subtype 2A receptor; 5-HT4 receptor, serotonin type 4 receptor; 5-HT7 receptor, serotonin type 7 receptor; BDNF, brain-derived neurotrophic factor; TrkB, tropomyosin tyrosine kinase receptor B; p75NTR, nerve growth factor receptor; rPol_II (RNA polymerase II), DNA-dependent RNA polymerase 2; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; RT, reverse transcription; PCR, polymerase chain reaction.

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Alsallum, M., Kaminskaya, Y.P., Tsybko, A.S. et al. Patterns of Expression of the Key Genes of the BDNF System and Serotonin Receptors in the Brain of OXYS Rats in the Development of the Signs of Alzheimer’s Disease. Adv Gerontol 13, 84–93 (2023). https://doi.org/10.1134/S207905702360026X

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