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A Study of Neurodegenerative Changes in the CA1 Region of the Dorsal Hippocampus in Adult Rats with Prenatal Hyperhomocysteinemia

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Abstract

The work is devoted to the study of neurodegenerative changes in the ultrastructural organization of hippocampal CA1 in adult rats that have suffered prenatal hyperhomocysteinemia (pHHC). Electron microscopy in the neural networks of the CA1 region of the dorsal hippocampus in adult rats with pHHC, in contrast to control animals, revealed signs of pathological changes: degeneration of pyramidal neurons and destruction of the myelin sheath of axons, as well as destruction of the axial cylinders of basal and apical dendrites directed from a pyramidal layer of neurons in the direction of tractus temporammonic or Schaffer collaterals, respectively. In control animals, on the distal branches of dendrites in the layers of the stratum oriens and stratum radiatum, using the Golgi method, a dense network of varicose dendritic extensions was identified, providing an increase in the area of synaptic contacts. In rats that have undergone pHHC, significant destructive changes are found in these dendritic varicosities: destruction of mitochondrial cristae and the appearance of dilated cisterns. In adult rats with pHHC, it completely eliminates the preference for the smell of valerian, which is normally a physiologically significant stimulus, which indicates a negative effect of pHHC on the functioning of the olfactory analyzer, the activity of which is closely connected with the hippocampus. The obtained facts indicate the detrimental effect of homocysteine on the structure and interneuronal connections in the nervous tissue of the CA1 region of the dorsal hippocampus, as a morphological substrate for the integration of stimuli entering it.

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ACKNOWLEDGMENTS

The authors thank A.V. Mikhel (Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences (SIEPB), St. Petersburg) for assistance in formulating the pHHC model. Electron microscopy was carried out using the equipment of the Center for Collective Use of the SIEPB using equipment for physiological, biochemical, and molecular biological research.

Funding

This work was financed from the budget of the SIEPB, state order no. 075-00967-23-00). No additional grants were received to conduct or direct this specific study.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    N. L. Tumanova, D. S. Vasiliev & N. M. Dubrovskaya

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  1. N. L. Tumanova
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  2. D. S. Vasiliev
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  3. N. M. Dubrovskaya
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Contributions

N. Tumanova: work idea and experiment planning, writing and editing text. N. Tumanova, D. Vasiliev, N. Dubrovskaya: data collection and processing. Text and figures were approved by all coauthors.

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Correspondence to D. S. Vasiliev.

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The authors of this work declare that they have no conflicts of interest

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All studies were conducted in accordance with the principles of biomedical ethics as set out in the 1964 Declaration of Helsinki and its subsequent amendments. They were also approved by the Ethics Committee of the SIEPB Institute of Evolutionary Physiology and Biochemistry (St. Petersburg, Russia), protocol no. 3/2020 dated March 18, 2020.

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Dedicated to the 90th anniversary of Margarita Gennadievna Belekhova, a wonderful person, researcher, and evolutionary biologist

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Abbreviations: HHC—hyperhomocysteinemia; pHHC—prenatal HHC; GO—oligodendrocyte glycoprotein; ANOVA—analysis of variance.

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Tumanova, N.L., Vasiliev, D.S. & Dubrovskaya, N.M. A Study of Neurodegenerative Changes in the CA1 Region of the Dorsal Hippocampus in Adult Rats with Prenatal Hyperhomocysteinemia. Cell Tiss. Biol. 18, 199–210 (2024). https://doi.org/10.1134/S1990519X23700116

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