Effect of non-selective NO-synthase inhibitor administered during pregnancy on the development of the cerebral cortex in 20-day-old rat pups
https://doi.org/10.47093/2218-7332.2023.14.3.37-44
Abstract
Aim. To study the morphology of neurons in the cerebral cortex of rat pups on day 20 under conditions of administration of a nitric oxide synthase inhibitor (NOS) during placentation.
Materials and methods. Outbred white female rats (n = 12) were randomly divided into 2 groups of 6 rats each. On the 11th day of pregnancy, the experimental group received a single intramuscular injection of N(omega)-nitro-L-arginine methyl ester (L NAME) at a dose of 25 mg/kg, in the control group – once intramuscularly 0.9% NaCl solution. Born rat pups were randomly selected one from the mother. On the 20th day, after medical euthanasia, the brain was collected. In the anterior part of the frontal cortex, we studied the density and area of neurons, the size and shape of perikarya and the severity of their staining with toluidine blue.
Results. In the experimental group of 20-day-old rat pups, compared to the control group, the density and area of neurons were less by 10% (p > 0.05) and 22% (p > 0.05), respectively, the shape of the perikarya also changed to elongated, the elongation factor increased by 0.3 units. (p < 0.05) and there was a sixfold increase in the proportion of hyperchromic neurons (p < 0.05), hyperchromic wrinkled (p < 0.001) neurons appeared, which were absent in control animals.
Conclusion. Morphological changes in neurons of the cerebral cortex in rat pups born from females who received a NOS inhibitor during placentation may be a consequence of a decrease in the formation of nitric oxide in the neurons themselves and in the endothelium of the vessels supplying the brain
About the Authors
T. S. RusakBelarus
Tatiana S. Rusak - Department of Pathological Physiology named after D.A. Maslakov
80, Gorky str., Grodno, 230009
Tel.: +375 29 284-68-74
N. Ye. Maksimovich
Belarus
Nataliya Ye. Maksimovich - Dr. of Sci. (Medicine), Professor, Head of the Department of Pathological Physiology named after D.A. Maslakov
80, Gorky str., Grodno, 230009
E. I. Bon
Belarus
Elizaveta I. Bon - Cand. of Sci. (Biology), Associate Professor, Department of Pathological Physiology named after D.A. Maslakov
80, Gorky str., Grodno, 230009
A. D. Bernatskaya
Belarus
Anna D. Bernatskaya - student
80, Gorky str., Grodno, 230009
A. S. Kusmartseva
Belarus
Angelina S. Kusmartseva - student
80, Gorky str., Grodno, 230009
References
1. Tricoire L., Vitalis T. Neuronal nitric oxide synthase expressing neurons: a journey from birth to neuronal circuits. Front Neural Circuits. 2012 Dec 5; 6: 82. https://doi.org/10.3389/fncir.2012.00082. PMID: 23227003; PMCID: PMC3514612
2. Dagdeviren M. Role of nitric oxide synthase in normal brain function and pathophysiology of neural diseases. Nitric oxide synthase – simple enzyme-complex roles. InTech; 2017. 248 p. https://dx.doi.org/10.5772/67267. ISBN 978-953-51-4837-1
3. Leon R.L., Mir I.N., Herrera C.L., et al. Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes. Pediatr. Res. 2022. 91(4): 787–794. https:// doi.org/10.1038/s41390-021-01521-7. Epub 2021 Apr 16. PMID: 33864014; PMCID: PMC9064799
4. Picón-Pagès P., Garcia-Buendia J., Muñoz F.J. Functions and dysfunctions of nitric oxide in brain. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 2019; 1865(8): 1949– 1967. https://doi.org/10.1016/j.bbadis.2018.11.007
5. Sidorova I.S., Nikitina N.A., Unanyan A.L., Ageev M.B.. Development of the fetal brain and the influence of prenatal damaging factors on the main stages of neurogenesis. Russian Bulletin of the ObstetricianGynecologist. 2022; 22(1): 35–44 (In Russian). https://doi.org/10.17116/rosakush20222201135
6. Kratimenos P., Penn A.A. Placental programming of neuropsychiatric disease. Pediatr. Res. 2019. 86(2): 157–164. https://doi.org/10.1038/s41390-019-0405-9. Epub 2019 Apr 19. PMID: 31003234
7. Dambrova M., Chlopicki S., Liepinsh E., et al. The methylester of gamma-butyrobetaine, but not gamma-butyrobetaine itself, induces muscarinic receptor-dependent vasodilatation. Naunyn Schmiedebergs Arch Pharmacol. 2004 May; 369(5): 533–539. https://doi.org/10.1007/s00210-004-0925-6. Epub 2004 Apr 2. PMID: 15060760
8. Szpera-Gozdziewicz A., Breborowicz G.H. Endothelial dysfunction in the pathogenesis of pre-eclampsia. Front. Biosci. 2014; 19(5): 734–746. https://doi.org/10.2741/4240
9. Moran M.C., Mulcahy C., Zombori G., et al. Placental volume, vasculature and calcification in pregnancies complicated by pre-eclampsia and intra-uterine growth restriction. Eur J Obstet Gynecol Reprod Biol. 2015 Dec; 195: 12–17. https://doi.org/10.1016/j.ejogrb.2015.07.023. Epub 2015 Aug 7. PMID: 26461962
10. Kaptilnyy V.A., Reyshtat D.Yu. Preeclampsia: definition, new in pathogenesis, guidelines, treatment and prevention. V.F. Snegirev Archives of Obstetrics and Gynecology. 2020; 7(1): 19–30 (In Russian). https://doi.org/10.18821/2313-8726-2020-7-1-19-30
11. Gureev V.V., Korokin M.V., Golubev I.V., et al. Correction of functional disorders in ADMA-like preeclampsia with derivatives of the peptide imitating erythropoietin α-helix B. Kursk Scientific and Practical Bulletin “Man and His Health”. 2020; (2): 42–49 (In Russian). https://doi.org/10.21626/vestnik/2020-2/06
12. Gatford K.L., Andraweera P.H., Roberts C.T., Care A.S. Animal models of preeclampsia: causes, consequences, and interventions. Hypertension. 2020 Jun; 75(6): 1363–1381. https://doi.org/10.1161/HYPERTENSIONAHA.119.14598. Epub 2020 Apr 6. PMID: 32248704
13. Klimov V.A. The fetoplacental endothelium in physiological and abnormal pregnancy. Obstetrics and Gynecology. 2008. 2: 7–9 (In Russian).
14. de Souza C.O., Peraçoli M.T.S., Weel I.C., et al. Hepatoprotective and anti-inflammatory effects of silibinin on experimental preeclampsia induced by L-NAME in rats. Life Sciences. 2012; 91(5–6): 159–165. https://doi.org/10.1016/j.lfs.2012.06.036
15. Muzyko E.A., Perfilova V.N., Kustova M.V., et al. Long-term consequences in the offspring born by rats with experimental preeclampsia. Medical News of North Caucasus. 2020; 15(3): 355–359 (In Russian). https://doi.org/10.14300/mnnc.2020.15084
16. Lotfullina N., Khazipov R. Ethanol and the developing brain: inhibition of neuronal activity and Neuroapoptosis. Neuroscientist. 2018 Apr; 24(2): 130–141. https://doi.org/10.1177/1073858417712667. Epub 2017 Jun 5. PMID: 28580823
17. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. 7th Edition, 2013. Hardback ISBN: 9780123919496. eBook ISBN: 9780124157521
18. Bon E.I., Maksimovich N.Ye., Zimatkin S.M. Morphological changes in the rats’ parietal cortex after subtotal cerebral ischemia and on the background of L-NAME administration. Vestnik VGMU. 2019; 18(1): 14–20 (In Russian). https://doi.org/10.22263/2312-4156.2019.1.14
19. Rusak T.S., Bon E.I., Maksimovich N.Ye, Martsun P.V. Effect of administration of a non-selective No Synthase inhibitor during pregnancy on cortical development in newborn rats. J Psych and Neuroche Res. 2023; 1(1): 01–03.
20. Bulanov N.М., Suvorov A.Yu., Blyuss O.B., et al. Basic principles of descriptive statistics in medical research. Sechenov Medical Journal. 2021; 12(3): 4–16 (In Russian). https://doi.org/10.47093/2218-7332.2021.12.3.4-16
21. Maksimovich N.E. Proposal on the nitroxidergic system of the brain (the role of extraneuronal sources). Journal of Grodno State Medical University. 2015; 1(5): 3–5. https://journalgrsmu.by/index.php/ojs/article/view/1631
22. Baracskay P., Szepesi Z., Orbán G., et al. Generalization of seizures parallels the formation of “dark” neurons in the hippocampus and pontine reticular formation after focal-cortical application of 4-aminopyridine (4-AP) in the rat. Brain Res. 2008. 1228: 217–228. https://doi.org/10.1016/j.brainres.2008.06.044
23. Bon E.I., Maksimovich N.Ye., Zimatkin S.M. Morphological features of parietal cortex and hippocampus neuron of rats following subtotal cerebral ischemia associated with omega-3 polyunsaturated fatty acids injection. Sibirskiy nauchnyy meditsinskiy zhurnal = Siberian Scientific Medical Journal. 2020; 40(3): 34–40 (In Russian). https://doi.org/10.15372/SSMJ20200305
24. Zimatkin S.M., Bon’ E.I. Dark Neurons of the brain. Neurosci Behav Physi. 2018; 48: 908–912. https://doi.org/10.1007/s11055-018-0648-7
25.
Supplementary files
![]() |
1. The ARRIVE guidelines 2.0: author checklist | |
Subject | ||
Type | Other | |
Download
(105KB)
|
Indexing metadata ▾ |