Study of neurodegenerative changes in the CA1 area of the dorsal hippocampus in adult rats after prenatal hyperhomocysteinemia

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The work is devoted to the study of neurodegenerative changes in the ultrastructural organization in CA1 of the hippocampus in adult rats subjected to prenatal hyperhomocysteinemia (pHHC). Electron microscopy revealed signs of pathological changes in the CA1 neural networks of the dorsal hippocampus in adult pHHC rats, unlike in control ones: cell degeneration, destruction of the myelin sheath of axons, and destruction of axial cylinders of basal and apical dendrites directed from the pyramidal neurons to the Schaffer collaterals and the temporo-ammonic tractus. In control animals, a dense network of varicose extensions in the distal branches of the dendrites in the stratum oriens and stratum radiatum layers was detected using the Golgi method, providing an increased area for synaptic contacts. In pHHC rats, significant destructive changes are found in these dendritic varicosities: destruction of mitochondrial cristae and appearance of huge cisterns. In adult rats, pHHC completely negated the preference for the smell of valerian, which is a physiologically significant stimulus in the norm, indicating the negative effect of pHHC on the work of the olfactory analyzer, whose activity is closely connected with the hippocampus. These findings indicate the deleterious effect of homocysteine on the formation of the dorsal hippocampus as a morphological substrate for the integration of the incoming impulses.

Full Text

Restricted Access

About the authors

N. L. Tumanova

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: dvasilyev@bk.ru
Russian Federation, St. Petersburg

D. S. Vasiliev

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Author for correspondence.
Email: dvasilyev@bk.ru
Russian Federation, St. Petersburg

N. M. Dubrovskaya

Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

Email: dvasilyev@bk.ru
Russian Federation, St. Petersburg

References

  1. Арутюнян А.В., Милютина Ю.П., Залозняя И.В., Пустыгина А.В., Козина Л.С., Кореневский А.В. Использование различных экспериментальных моделей гипергомоцистеинемии в нейрохимических исследованиях. Нейрохимия. 2012. Т. 29. № 2. С. 83. (Arutjunyan A., Kozina L., Stvolinskiy S., Bulygina Y., Mashkina A., Khavinson V. 2012. Pinealon protects the rat offspring from prenatal hyperhomocysteinemia. Int. J. Clin. Exper. Med. 5(2). Р. 179).
  2. Белехова М. Г., Туманова Н. Л. Структурные основы слухо-соматического взаимодействия в мозгу черепахи Еmys orbicularis. Дендритный обмен между ядрами. Журнал эвол. биохим. и физиол. 1988. Т. 24. № 3. С. 326. (Belekhova M.G., Tumanova N.L. 1988. Structural bases of audio-somatic interactions in turtle Еmys orbicularis brain. Dendrite exchange between nuclei. J. Evol. Biochem. Physiol. (Russ.) V. 24. P. 326.)
  3. Борякова Е.Е., Гладышева О.С., Крылов В.Н. Возрастная динамика обонятельной чувствительности у самок лабораторных мышей и крыс к запаху изовалериановой кислоты. Сенсорные системы. 2007. Т. 21. № 4. С. 341. (Boryakova E.E., Gladysheva O.S., Krylov V.N. 2007. Age dynamics of olfactory sensitivity in female laboratory mice and rats to the smell of isovaleric acid. Sensory systems. V. 21. P. 341.)
  4. Мельник С.А., Гладышева О.С., Крылов В.Н. Возрастные изменения обонятельной чувствительности самцов мышей к запаху изовалериановой кислоты. Сенсорные системы. 2009. Т. 23. № 2. С. 151. (Mel’nik S.A., Gladysheva O.S., Krylov V.N. 2009. Age-related changes in the olfactory sensitivity of male mice to the smell of isovaleric acid. Sensory systems. V. 23. P. 151.)
  5. Мельник С.А., Гладышева О.С., Крылов В.Н. Влияние предварительного воздействия паров изовалериановой кислоты на обонятельную чувствительность самцов домовой мыши. Сенсорные системы. 2012. Т. 26. № 1. С. 52. (Mel’nik S.A., Gladysheva O.S., Krylov V.N. 2012. Influence of preliminary exposure to isovaleric acid vapors on the olfactory sensitivity of male house mice. V. 26 P. 52.)
  6. Allen T.A., Fortin N.J. 2013. The evolution of episodic memory. Proc. Natl. Acad. Sci. USA. V. 110. P. 10379.
  7. Berger T., Rubner P., Schautzer F., Egg R., Ulmer H., Mayringer I., Dilitz E., Deisenhammer F., Reindl M. 2003. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. New England J. Med. V. 349. 139. doi: 10.1056/NEJMoa022328
  8. Bergmann E., Zur G., Bershadsky G., Kahn I. 2016. The organization of mouse and human corticohippocampal networks estimated by intrinsic functional connectivity. Cereb. Cortex. 26. Р. 4497–4512. https://doi.org/10.1093/cercor/bhw327
  9. Buckner R.L., Krienen F.M. 2013. The evolution of distributed association networks in the human brain. Trends Cogn. Sci. V. 17. P. 648. https://doi.org/10.1016/j.tics.2013.09.017
  10. Dubrovskaya N.M., Vasilev D.S., Tumanova N.L., Alekseeva O.S., Nalivaeva N.N. 2022. Prenatal hypoxia impairs olfactory function in postnatal ontogeny in rats. Neurosci. Behav. Physiol. V. 52. P. 262. https://doi.org/10.1007/s11055-022-01233-3
  11. Gass N., Schwarz A.J., Sartorius A., Schenker E., Risterucci C., Spedding M., Zheng L., Meyer-Lindenberg A., Weber-Fahr W. 2014. Sub-anesthetic ketamine modulates intrinsic BOLD connectivity within the hippocampal-prefrontal circuit in the rat. Neuropsychopharmacol. V. 39. P. 895.
  12. Ketelslegers I.A., Van Pelt D.E., Bryde S., Neuteboom R.F., Catsman-Berrevoets C.E., Hamann D., Hintzen R.Q. 2015. Anti-MOG antibodies plead against MS diagnosis in an acquired demyelinating syndromes cohort. Multiple Sclerosis. V. 21. P. 1513. doi: 10.1177/1352458514566666
  13. Kezuka T., Usui Y., Yamakawa N., Matsunaga Y., Matsuda R., Masuda M., Utsumi H., Tanaka K., Goto H. 2012. Relationship between NMO-antibody and anti-MOG antibody in optic neuritis. J. Neuro-Ophthalmol. V. 32. P. 107. doi: 10.1097/WNO.0b013e31823c9b6c
  14. Kitley J., Woodhall M., Waters P., Leite M.I., Devenney E., Craig J., Palace J., Vincent A. 2012. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype. Neurology. 79 (12). Р. 1273–1277. doi: 10.1212/WNL.0b013e31826aac4e
  15. Liska A., Galbusera A., Schwarz A.J., Gozzi A. 2015. Functional connectivity hubs of the mouse brain. Neuroimage. V. 115. P. 281. https://doi.org/10.1016/j.neuroimage.2015.04.033
  16. Lu J., Testa N., Jordan R., Elyan R., Kanekar S., Wang J., Eslinger P., Yang Q., Zhang B., Karunanayaka P. 2019. Functional connectivity between the resting-state olfactory network and the hippocampus in Alzheimer’s disease. Brain Sci. V. 9. P. 338. https://doi.org/10.3390/brainsci9120338
  17. Matsumoto-Oda A., Oda R., Hayashi Y., Murakami H., Maeda N., Kumazaki K., Shimizu K., Matsuzawa T. 2003. Vaginal fatty acids produced by chimpanzees during menstrual cycles. Folia Primatol (Basel). V. 74. P. 75. https://doi.org/10.1159/000070000
  18. Mechling A.E., Hübner N.S., Lee H-L., Hennig J., von Elverfeldt D., Harsan L-A. 2014. Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI. Neuroimage. V. 96. P. 203. https://doi.org/10.1016/j.neuroimage.2014.03.078
  19. Müller-Schwarze D., Müller-Schwarze C., Singer A.G., Silverstein R.M. 1974. Mammalian pheromone: identification of active component in the subauricular scent of the male pronghorn. Science. V. 183. P. 860. https://doi.org/10.1126/science.183.4127.860
  20. Paxinos G., Watson C. 2007. The rat brain in stereotaxic coordinates. Elsevier: Amsterdam-Boston.
  21. Postnikova T.Y., Amakhin D.V., Trofimova A.M., Tumanova N.L., Dubrovskaya N.M., Kalinina D.S., Kovalenko A.A., Shcherbitskaia A.D., Vasilev D.S., Zaitsev A.V. 2022. Maternal Hyperhomocysteinemia Produces Memory Deficits Associated with Impairment of Long-Term Synaptic Plasticity in Young Rats. Cells. V. 12. P. 58. https://doi.org/10.3390/cells12010058
  22. Ribaut-Barassin C., Dupont J-L., Haeberlé a-M., Bombarde G., Huber G., Moussaoui S., Mariani J., Bailly Y. 2003. Alzheimer’s disease proteins in cerebellar and hippocampal synapses during postnatal development and aging of the rat. Neurosci. V. 120. P. 405. doi: 10.1016/S0306-4522(03)00332-4
  23. Rice D., Barone S. 2000. Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environ. Health Perspect. V. 108. P. 511. https://doi.org/10.1289/ehp.00108s3511
  24. Schwarz A.J., Gass N., Sartorius A., Zheng L., Spedding M., Schenker E., Risterucci C., Meyer-Lindenberg A., Weber-Fahr W. 2013. The low-frequency blood oxygenation level-dependent functional connectivity signature of the hippocampal-prefrontal network in the rat brain. Neurosci. V. 228. P. 243. https://doi.org/10.1016/j.neuroscience.2012.10.032
  25. Shcherbitskaia A.D., Vasilev D.S., Milyutina Y.P., Tumanova N.L., Mikhel A.V., Zalozniaia I.V., Arutjunyan A.V. 2021. Prenatal hyperhomocysteinemia induces glial activation and alters neuroinflammatory marker expression in infant rat hippocampus. Cells. V. 10. P. 1536. https://doi.org/10.3390/cells10061536
  26. Vasilev D.S., Shcherbitskaia A.D., Tumanova N.L., Mikhel A.V., Milyutina Y.P., Kovalenko A.A., Dubrovskaya N.M., Inozemtseva D.B., Zalozniaia I.V., Arutjunyan A.V. 2023. Maternal hyperhomocysteinemia disturbs the mechanisms of embryonic brain development and its maturation in early postnatal ontogenesis. Cells. V. 12. P. 189. https://doi.org/10.3390/cells12010189
  27. Zhou G., Olofsson J.K., Koubeissi M.Z., Menelaou G., Rosenow J., Schuele S.U., Xug P., Voss J.L., Lane G., Zelano C. 2021. Human hippocampal connectivity is stronger in olfaction than other sensory systems. Progress Neurobiol. V. 201. P. 102027. https://doi.org/10.1016/j.pneurobio.2021.102027

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Neurodegenerative changes in the cells of the pyramidal layer of the CA1 region of the dorsal hippocampus in adult rats that have undergone PHGC (b, d-h) in comparison with controls (a, c); a, b - microphotographs of the CA1 field of the hippocampus in control (a) and PHGC-treated (b) rats. Nissl staining, scale bar: 30 μm. Arrows show pyramidal neurons in the state of chromatolysis; N - neurons, D - dendrites. c-h - electronograms of the CA1 region of rat hippocampus in control (c) and with pGHC (d-h); chromatolysis (Chr, d), neurofilament-type cellular degeneration (e, f), neurofilament outgrowth in the neuron outgrowth (f), activation of astrocytic glia (g) and autophagosome in the neuron cytoplasm (h) are shown. Ml - myelinated fibers, M - mitochondria, Nf - neurofilaments, Ag - astrocytic glia outgrowths, Af - autophagosomes

Download (1MB)
Indexing metadata
3. Fig. 2. Destructive changes in basal dendrites of the CA1 region of the dorsal hippocampus. Electronograms of rats control (a-c) and with pGHC (d-j) at the age of P90. C - cisternae, CHR - chromatolysis, D - dendrites, M - mitochondria, N - neurons, S - synaptic terminals with contacts, Sp - dendritic spines, Vr - varicosities

Download (2MB)
Indexing metadata
4. Fig. 3. Destructive changes in apical dendrites of the CA1 region of the dorsal hippocampus. Electronograms of pGHC rats at the age of P90 (a-f). Ml - myelinated fibers, D - dendrites, M - mitochondria, Vr - varicosities, C - cisternae, S - synaptic terminals with contacts, Sp - dendritic spines

Download (965KB)
Indexing metadata
5. Fig. 4. Structural organization of basal and apical dendrites of pyramidal neurons of the CA1 region of the adult dorsal hippocampus of control rats: a - schematic representation of cytoarchitectonics of the CA1 region of the rat dorsal hippocampus; b-d - microphotographs of the CA1 region of the adult dorsal hippocampus (P90) of control rats. Golgi method, scale bar 10 μm, in the center there is a layer of pyramidal neurons (Str. pyramidale); c - varicose extensions on basal and apical dendrites of pyramidal neurons; d - powerful bundles of basal and apical dendrites with dendritic spicules and varicose extensions; e, f - quantitative analysis of varicose extensions (e) and dendritic spicules (f) on the section of basal (Str. oriens) and apical (Str. radiatum) dendrites of pyramidal neurons in control rats; mean values and their errors are shown. Denotations: Str. - stratum, N - neurons, AD - apical dendrites, D - dendrites, BD - basal dendrites, Vr - varicose extensions of dendrites, Sp - dendritic spines

Download (2MB)
Indexing metadata
6. Fig. 5. Effect of pGHC on myelination of nerve fibers in the field of rat dorsal hippocampus: electronograms of rats control (a) and with pGHC (b) at the age of P90. Ml - myelinated fibers, M - mitochondria; c-p - comparison of oligodendrocyte glycoprotein (GO, FITC luminescence) distribution in liver tissue (c) and CA1 region of hippocampus (d, e, g, h, h, k, l, n, o) of control rats (d, e, g, h) and pGHC rats (k, l, n, o) at the age of P20 (d, e, k, l) and P90 (g, h, n, o). Immunohistochemical staining, scale bar: 20 μm; c, negative control (GO+-liver - complete immunochemical reaction on liver tissue preparation of control rat at P20) with primary and secondary antibodies, scale bar: 40 μm; d, g, w, k, n - negative control (GO¯ - immunochemical reaction on hippocampal tissue preparation in the absence of primary antibodies); e, i, m, p - myelination index, units. units (difference in the luminescence brightness between the studied tissue section and the corresponding negative control GO¯) - results of densitometry of immunochemical staining of GO in the stratum stratum oriens (Str. ori.: e, i) and stratum raditum (Str. rad.: m, p) in rats at P20 (e, m) and P90 (i, p). Data are presented as mean and its error. Asterisks indicate differences between control group and with pGHC at P20 at P = 0.005 (**) and P = 0.0008 (***) (nonparametric Mann-Whitney test)

Download (1MB)
Indexing metadata
7. Fig. 6. Schematic of distribution of odorant odor preference indices by adult rats - control (a) and with pGHC (b). The indices are represented by multicolored sectors and are expressed by the number of approaches (mean value and its error) to the receptacle with the corresponding odorant of natural vegetable oil as a percentage of the total number of approaches to all receptacles. The sector corresponding to physiologically significant odor of valerian is marked with a black border. Dashed lines between sectors indicate statistically significant differences in preference indices between odorants in pGHC animals. The size of each sample is n = 15. One-factor ANOVA followed by post hoc Bonferroni analysis. * - preference for valerian odor relative to the other five odors is reliable at P < 0.0001; # - preference for wormwood odor relative to clove, and wormwood odor relative to valerian are reliable at P < 0.05

Download (233KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies