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PI3K/Akt/mTOR-immunoreactive neurons in the rat mediobasal hypothalamus during aging

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Abstract

The hypothalamus is the regulatory hub controlling homeostasis, reproduction, circadian rhythms and endocrine system. It is also involved in the regulation of senescence. The location of neurons containing phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase B (AKT), phosphorylated forms AKT (pAKT) and mTOR (pmTOR) was examined by immunohistochemistry in 2-, 6-, 12-, and 24-month-old male rats in the arcuate (ARN), dorsomedial (DMN) and ventromedial (VMN) hypothalamic nuclei. Results have shown that the components of PI3K-AKT-mTOR signaling changes differentially in the rat mediobasal hypothalamic nuclei with aging. There were no changes of PI3K expression during senescence. However, the percentage of pmTOR-immunoreactive (IR) neurons decreased in the ARN and DMN but not in the VMN with aging. Nevertheless, the percentage of AKT-IR hypothalamic cells significantly increased in the ARN, DMN and VMN, and the proportion of pAKT-IR neurons increased in the DMN and VMN with aging. Thus, in spite of some differences of the expression of PI3K-AKT-mTOR signaling components in separate mediobasal hypothalamic nuclei, AKT expression is upregulated and pmTOR is downregulated with aging. These findings confirm an importance of AKT and mTOR of key signaling components that are often impaired with senescence. The data obtained will also serve as a basis for future studies investigating mechanisms of the age-related diseases.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements and funding

This work was supported by Russian Science Foundation (Project No. 19–15-00039).

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Authors and Affiliations

  1. Department of Normal Physiology and Biophysics, Yaroslavl State Medical University, Ul. Revoliucionnaya 5, Yaroslavl, 150000, Russia

    Lydia G. Pankrasheva, Polina A. Anfimova, Konstantin Yu Moiseev, Elizaveta S. Shirina & Petr M. Masliukov

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  1. Lydia G. Pankrasheva
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  2. Polina A. Anfimova
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  3. Konstantin Yu Moiseev
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  4. Elizaveta S. Shirina
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Contributions

Methodology, software, validation, E.S.S.; formal analysis, investigation, P.A.A.; resources, data curation, L.G.P.; writing—original draft preparation, writing—review and editing, visualization, K.Y.M.; conceptualization, supervision, project administration, funding acquisition, P.M.M. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Petr M. Masliukov.

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The current study was approved by the Yaroslavl State Medical University. All procedures involving animals were conducted in accordance with the ethical standards of the institution.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Pankrasheva, L.G., Anfimova, P.A., Moiseev, K.Y. et al. PI3K/Akt/mTOR-immunoreactive neurons in the rat mediobasal hypothalamus during aging. Neurosci Behav Physi 53, 1319–1329 (2023). https://doi.org/10.1007/s11055-023-01504-7

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