Pathogenetic features of iNOS expression in the basal magnocellular nucleus of rats against the background of experimental neurodegeneration

Authors

DOI:

https://doi.org/10.14739/2310-1237.2024.2.303264

Keywords:

nitric oxide synthase, nitrosative stress, nitrites, neurodegeneration

Abstract

Aim. To characterize the features of iNOS expression in neurons of the basal magnocellular nucleus against the background of nitrosative stress during experimental colchicine-induced neurodegeneration.

Materials and methods. The study was conducted on 30 male Wistar rats. At the first stage of the experiment, cognitive impairments were modeled in rats (n = 10) by intracerebroventricular injection of colchicine, and compared with sham-operated and intact animal groups, the validity of the model was demonstrated using an 8-arm radial maze LE760 (PanLab Harvard Apparatus, Spain). Subsequently, the animals were euthanized with sodium thiopental, and the brain was removed for histological, immunofluorescence, and biochemical analyses.

Results. It was found that intracerebroventricular injection of colchicine compared to intact and sham-operated animals leads to disruption of histoarchitecture in the basal magnocellular nucleus of rats with a significant decrease in the Nissl substance area in neurons by 47.3 % and 35.9 %, respectively. At the same time, the level of nitrites in the brain homogenates of animals with experimental neurodegeneration exceeded the comparison groups almost 10 times (intact) and 7 times (sham-operated rats). Meanwhile, immunofluorescence investigation of iNOS expression in the basal magnocellular nucleus of rats with intracerebroventricular colchicine administration, compared to intact and sham-operated animals, revealed a significantly higher value of corrected total cell fluorescence by 22.7 % and 45.3 %, respectively. Simultaneously, it was established that experimental colchicine-induced neurodegeneration is accompanied by a significantly greater number of iNOS+ cells in the basal magnocellular nucleus compared to control groups.

Conclusions. Intracerebroventricular injection of colchicine to experimental rats is accompanied by morphological signs of neurodestruction in the basal magnocellular nucleus against the background of nitrosative stress. iNOS expression in rats after intracerebroventricular colchicine administration in the cells of the basal magnocellular nucleus is characterized by a higher enzyme content compared to intact and sham-operated animals. The area of immunopositive cells between experimental groups does not change statistically. Intracerebroventricular administration of colchicine to experimental rats is accompanied by an increase in the number of immunopositive cells for iNOS in the basal magnocellular nucleus.

Author Biographies

M. V. Danukalo, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

PhD, Associate Professor of the Department of Pathological Physiology with the Course of Normal Physiology

Yu. M. Kolesnyk, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, DSc, Professor of the Department of Pathological Physiology with the Course of Normal Physiology, Rector of Zaporizhzhia State Medical and Pharmaceutical University, Honored Science and Technology Figure of Ukraine

References

Rapaka D, Adiukwu PC, Bitra VR. Experimentally induced animal models for cognitive dysfunction and Alzheimer’s disease. MethodsX. 2022;9:101933. doi: https://doi.org/10.1016/j.mex.2022.101933

Som Chaudhury S, Nandi M, Kumar K, Ruidas B, Sur TK, Prasad P, et al. Rodent model preclinical assessment of pegylated block copolymer targeting cognition and oxidative stress insults of alzheimer’s disease. Mol Neurobiol. 2023;60(4):2036-50. doi: https://doi.org/10.1007/s12035-022-03194-7

Dhapola R, Kumari S, Sharma P, HariKrishnaReddy D. Insight into the emerging and common experimental in-vivo models of Alzheimer’s disease. Lab Anim Res. 2023;39(1):33. doi: https://doi.org/10.1186/s42826-023-00184-1

Oswald MJ, Han Y, Li H, Marashli S, Oglo DN, Ojha B, et al. Cholinergic basal forebrain nucleus of Meynert regulates chronic pain-like behavior via modulation of the prelimbic cortex. Nat Commun. 2022;13(1):5014. doi: https://doi.org/10.1038/s41467-022-32558-9

Soma S, Suematsu N, Sato AY, Tsunoda K, Bramian A, Reddy A, et al. Acetylcholine from the nucleus basalis magnocellularis facilitates the retrieval of well-established memory. Neurobiol Learn Mem. 2021;183:107484. doi: https://doi.org/10.1016/j.nlm.2021.107484

Byun J-I, Cha KS, Kim M, Lee W-J, Lee HS, Sunwoo J-S, et al. Association of nucleus basalis of Meynert functional connectivity and cognition in idiopathic rapid-eye-movement sleep behavior disorder. J Clin Neurol. 2022;18(5):562-70. doi: https://doi.org/10.3988%2Fjcn.2022.18.5.562

Aisen PS, Jimenez-Maggiora GA, Rafii MS, Walter S, Raman R. Early-stage alzheimer disease: Getting trial-ready. Nat Rev Neurol. 2022;18(7):389-99. doi: https://doi.org/10.1038/s41582-022-00645-6

Saini N, Singh D, Sandhir R. Bacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action. Metab Brain Dis. 2019;34(2):505-18. doi: https://doi.org/10.1007/s11011-018-0332-1

Sil S, Ghosh R, Sanyal M, Guha D, Ghosh T. A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular Colchicine Injection. J Immunotoxicol. 2015;13(2):181-90. doi: https://doi.org/10.3109/1547691X.2015.1030804

Balez R, Ooi L. Getting to no alzheimer’s disease: Neuroprotection versus neurotoxicity mediated by nitric oxide. Oxid Med Cell Longev. 2016;2016:3806157. doi: https://doi.org/10.1155/2016/3806157

Piacenza L, Zeida A, Trujillo M, Radi R. The superoxide radical switch in the biology of nitric oxide and peroxynitrite. Physiol Rev. 2022;102(4):1881-906. doi: https://doi.org/10.1152/physrev.00005.2022

Picón-Pagès P, Garcia-Buendia J, Muñoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis. 2019;1865(8):1949-67. doi: https://doi.org/10.1016/j.bbadis.2018.11.007

Danukalo MV, Kolesnyk YM, Hancheva OV. Contemporary comprehensive approaches to assessing the effectiveness of experimental model of neurodegenerative disorders with cognitive status changes. Modern medical technology. 2023;0(4):51-8. doi: https://doi.org/10.34287/MMT.4(59).2023.7

Paxinos G, Watson C. The Rat Brain in stereotaxic coordinates. London: Elsevier, Academic Press; 2018.

Zhu Y, Liu F, Zou X, Torbey M. Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods. J Neurosci Methods. 2015;254:73-9. doi: https://doi.org/10.1016/j.jneumeth.2015.07.022

Santa Cruz Biotechnology. Immunofluorescence Cell Staining [Internet]. www.scbt.com. [cited 2024 Jul 4]. Available from: https://www.scbt.com/resources/protocols/immunofluorescence-cell-staining

Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5(1):62-71. doi: https://doi.org/10.1006/niox.2000.0319

Holovanova IA, Bielikova IV, Liakhova NO. Osnovy medychnoi statystyky [Basics of medical statistics]. Poltava, Ukrainian Medical Stomatological Academy; 2017. Ukrainian. Available from: https://core.ac.uk/download/211228894.pdf

Sil S, Ghosh T, Ghosh R, Gupta P. Nitric oxide synthase inhibitor, aminoguanidine reduces intracerebroventricular colchicine induced neurodegeneration, memory impairments and changes of systemic immune responses in rats. J Neuroimmunol. 2017;303:51-61. doi: https://doi.org/10.1016/j.jneuroim.2016.12.007

Memudu AE, Adewumi AE. Alpha lipoic acid ameliorates scopolamine induced memory deficit and neurodegeneration in the Cerebello-hippocampal cortex. Metab Brain Dis. 2021;36(7):1729-45. doi: https://doi.org/10.1007/s11011-021-00720-9

Liang Y, Li S, Wen C, Zhang Y, Guo Q, Wang H, et al. Intrastriatal injection of colchicine induces striatonigral degeneration in mice. J Neurochem. 2008;106(4):1815-27. doi: https://doi.org/10.1111/j.1471-4159.2008.05526.x

Kumar A, Dogra S. Neuroprotective effect of Carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat. Pharmacol Biochem Behav. 2009;92(1):25-31. doi: https://doi.org/10.1016/j.pbb.2008.10.005

Moro MA, De Alba J, Leza JC, Lorenzo P, Fernández AP, Bentura ML, et al. Neuronal expression of inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain slices. Eur J Neurosci. 1998;10(2):445-56. doi: https://doi.org/10.1046/j.1460-9568.1998.00028.x

El Azab EF, Abdulmalek S. Amelioration of age-related multiple neuronal impairments and inflammation in high-fat diet-fed rats: The prospective multitargets of Geraniol. Oxid Med Cell Longev. 2022;2022:4812993. doi: https://doi.org/10.1155/2022/4812993

Pourbagher-Shahri AM, Farkhondeh T, Talebi M, Kopustinskiene DM, Samarghandian S, Bernatoniene J. An overview of no signaling pathways in aging. Molecules. 2021;26(15):4533. doi: https://doi.org/10.3390/molecules26154533

Doherty GH. Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories. Neurosci Bull. 2011;27(6):366-82. doi: https://doi.org/10.1007/s12264-011-1530-6

Chen M-H, Wang T-J, Chen L-J, Jiang M-Y, Wang Y-J, Tseng G-F, et al. The effects of astaxanthin treatment on a rat model of alzheimer’s disease. Brain Res Bull. 2021;172:151-63. doi: https://doi.org/10.1016/j.brainresbull.2021.04.020

Bortolanza M, Cavalcanti-Kiwiatkoski R, Padovan-Neto FE, da-Silva CA, Mitkovski M, Raisman-Vozari R, et al. Glial activation is associated with L-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson’s disease. Neurobiol Dis. 2015;73:377-87. doi: https://doi.org/10.1016/j.nbd.2014.10.017

Additional Files

Published

2024-08-30

How to Cite

1.
Danukalo MV, Kolesnyk YM. Pathogenetic features of iNOS expression in the basal magnocellular nucleus of rats against the background of experimental neurodegeneration. Pathologia [Internet]. 2024Aug.30 [cited 2024Oct.15];21(2):93-9. Available from: http://pat.zsmu.edu.ua/article/view/303264

Issue

Section

Original research