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Changes in the Rat Hippocampal Neurogenic Niche under Hypoxic Exposure

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Abstract

The hippocampus is one of the brain structures most vulnerable to hypoxia. The cellular pool in the hippocampal subgranular zone (SGZ) neurogenic niche is maintained by the adaptive mechanisms, such as functional changes in the mitochondrial respiratory chain complexes and the reactivity of astroglia that provides structural and metabolic support for neurons. To reveal the dynamics of adaptive changes in neurons and glia of the hippocampal dentate gyrus in response to single (60 min) and repeated (8 and 20 bouts) intermittent hypobaric hypoxia exposures (5000 m equivalent to 10.5% O2), the localization and content of mitochondrial respiratory Complex IV cytochrome c oxidase subunit 1 (MTCO1), astrocyte markers glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP), as well as the immature neuron marker doublecortin (DCX), were studied in low-resistant rats by immunomorphological methods. After a single hypoxic exposure, the MTCO1 content significantly increased in neurons, while after 8 hypoxic episodes, the GS level increased in astrocytes. Changes in the latter were most prominent in the astrocytic processes, indicative of hypoxia-induced GS redistribution. The number of DCX-positive neurons in the SGZ significantly decreased after 20 hypoxic episodes. At the same time, DCX-positive glia-like cells were found in the hippocampal polymorphic layer, while GFAP labeling revealed an increase in the number of astrocytes, which may be partly due to a shift in the direction of cell differentiation in the neurogenic niche. Thus, hypoxia first intensifies mitochondrial respiratory chain activity in the neurons of the hippocampal granular cell layer, followed by the activation of astrocytes that modulate glutamate metabolism. The relationship between the dynamics of adaptive energy metabolism reactions in neurons and glia and changes in neurogenesis after 20 hypoxic episodes suggests that repeated (long-term) hypoxia promotes a shift in the differentiation of SGZ neural progenitors toward astroglia. However, this issue requires further investigation to identify the nature of DCX-positive cells more accurately.

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Funding

This work was state budget funded.

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Authors and Affiliations

  1. Research Center of Neurology, Moscow, Russia

    E. N. Fedorova, D. N. Voronkov, A. V. Egorova, T. I. Baranich & V. S. Sukhorukov

  2. Pirogov Russian National Medical University, Moscow, Russia

    E. N. Fedorova, A. V. Egorova, T. I. Baranich, V. V. Glinkina & V. S. Sukhorukov

  3. Research Institute of General Pathology and Pathophysiology, Moscow, Russia

    E. L. Germanova & L. D. Lukyanova

Authors
  1. E. N. Fedorova
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  2. D. N. Voronkov
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  3. A. V. Egorova
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  4. T. I. Baranich
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  5. V. V. Glinkina
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Contributions

Conceptualization and experimental design (E.N.F., D.N.V., A.V.E., E.L.G.), data collection, processing and analysis (E.N.F., D.N.V., A.V.E.), writing and editing the manuscript (E.N.F., D.N.V., A.V.E., T.I.B., V.V.G., L.D.L., V.S.S.).

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Correspondence to E. N. Fedorova.

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COMPLIANCE WITH ETHICAL STANDARDS

All applicable international, national and/or institutional principles of animal care and use were observed. All experimental procedures performed with the use of animals complied with the ethical standards approved by legal acts of the Russian Federation, the principles of the Basel Declaration, and the recommendations by the local Ethics Committee at the Research Center of Neurology (Meeting minutes nos. 10—7/20 of 27.11.2020).

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The authors declare that they have no conflict of interest related to the publication of this article.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2023, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2023, Vol. 59, No. 4, pp. 319–331https://doi.org/10.31857/S0044452923040022.

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Fedorova, E.N., Voronkov, D.N., Egorova, A.V. et al. Changes in the Rat Hippocampal Neurogenic Niche under Hypoxic Exposure. J Evol Biochem Phys 59, 1086–1099 (2023). https://doi.org/10.1134/S0022093023040075

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