Ukr.Biochem.J. 2026; Volume 98, Issue 3, May-Jun, pp. 44-53
doi: https://doi.org/10.15407/ubj98.03.044
Nitric oxide system parameters in the basal magnocellular nucleus of the rat brain following intracerebroventricular administration of colchicine
, , ,
1Department of Pathological Physiology with the Course of Normal Physiology,
Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine;
2Department of Physical, Colloid and Analytical Chemistry,
Zaporizhzhia State Medical and Pharmaceutical University, Zaporizhzhia, Ukraine;
*e-mail: danukalo.m.v@zsmu.edu.ua
Received: 25 February 2026; Revised: 18 May 2026;
Accepted: 29 May 2026; Available on-line: 18 June 2026
Background. The basal magnocellular nucleus (BMN) is a brain structure that provides cholinergic innervation of the neocortex. Disruption of BMN functional activity is observed in many neurodegenerative diseases. One of the key regulatory systems of neuronal activity in the brain is the nitric oxide (NO) system, however, the interactions among NO system components during neurodestruction have not yet been fully elucidated. Objective. The aim of the study was to determine L-arginine, nitrites, nitrotyrosine levels, iNOS, and nNOS expression in the rat BMN in a model of colchicine-induced neurodestruction. Methods. The study involved 30 male Wistar rats divided into three groups: intact, sham-operated with intracerebroventricular (ICV) administration of 3 μl of NaCl, and colchicine group with ICV injection of colchicine (15 μg/3 μl NaCl). ICV injections were carried out using a digital stereotaxic apparatus. Two weeks after colchicine administration, the animals developed cognitive deficits evidenced by behavioral testing. Following euthanasia, the brain tissue was rapidly removed for further processing. iNOS and nNOS expression was assessed via immunofluorescence microscopy, nitric oxide metabolites were measured using the Griess method, L-arginine concentration via HPLC-MS, and nitrotyrosine level via ELISA. Results. Intracerebroventricular administration of colchicine was followed by a decrease in L-arginine level accompanied by a significant increase in NO metabolites and nitrotyrosine levels in the BMN of rats. Immunofluorescent analysis revealed increased density of iNOS-positive and a progressive reduction of nNOS-positive cells in the BMN cell population of colchicine-injected rats. Correlation analysis confirmed that NO-system imbalance plays a significant role in neurodestruction. Conclusions. Colchicine-induced neurodestruction in the rat BMN is associated with imbalance of the nitric oxide system characterized by decreased L-arginine levels, increased NO metabolites and nitrotyrosine content, elevated iNOS expression, and reduced nNOS-positive cell density. These alterations may contribute to neurodegenerative processes in the BMN.
Keywords: brain, colchicine, iNOS, L-arginine, neurodegeneration, nitric oxide system, nitrites, nitrotyrosine, nNOS
References:
- Soma S, Suematsu N, Sato AY, Tsunoda K, Bramian A, Reddy A, Takabatake K, Karube F, Fujiyama F, Shimegi S. Acetylcholine from the nucleus basalis magnocellularis facilitates the retrieval of well-established memory. Neurobiol Learn Mem. 2021;183:107484. PubMed, CrossRef
- Zhu HY, Hong FF, Yang SL. The Roles of Nitric Oxide Synthase/Nitric Oxide Pathway in the Pathology of Vascular Dementia and Related Therapeutic Approaches. Int J Mol Sci. 2021;22(9):4540. PubMed, PubMedCentral, CrossRef
- Azargoonjahromi A. Dual role of nitric oxide in Alzheimer’s disease. Nitric Oxide. 2023;134-135:23-37. PubMed, CrossRef
- Yang Q, Kang ZH, Zhang J, Qu F, Song B. Neuroprotective Effects of Isoquercetin: An In Vitro and In Vivo Study. Cell J. 2021;23(3):355-365. PubMed, PubMedCentral, CrossRef
- Doulah A, Mahmoodi G, Pourmahdi Borujeni M. Evaluation of the pre-treatment effect of Centella asiatica medicinal plants on long-term potentiation (LTP) in rat model of Alzheimer’s disease. Neurosci Lett. 2020;729:135026. PubMed, CrossRef
- 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. PubMed, CrossRef
- Paxinos G, Watson C. The Rat Brain in stereotaxic coordinates. London: Elsevier, Academic Press; 2018.
- Danukalo MV, Kolesnyk YM, Hancheva OV. Contemporary comprehensive approaches to assessing the effectiveness of experimental model of neurodegenerative disorders with cognitive status changes. Mod Med Technol. 2023;(4):51-58. CrossRef
- Santa Cruz Biotechnology. Immunofluorescence Cell Staining [Internet]. www.scbt.com. Available from: https://www.scbt.com/resources/protocols/immunofluorescence-cell-staining.
- Farahani A, Farahani A, Kashfi K, Ghasemi A. Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms. Pharmacol Res. 2025;216:107781. PubMed, PubMedCentral, CrossRef
- Kan MJ, Lee JE, Wilson JG, Everhart AL, Brown CM, Hoofnagle AN, Jansen M, Vitek MP, Gunn MD, Colton CA. Arginine deprivation and immune suppression in a mouse model of Alzheimer’s disease. J Neurosci. 2015;35(15):5969-5982. PubMed, PubMedCentral, CrossRef
- Fernando V, Zheng X, Walia Y, Sharma V, Letson J, Furuta S. S-Nitrosylation: An Emerging Paradigm of Redox Signaling. Antioxidants (Basel). 2019;8(9):404. PubMed, PubMedCentral, CrossRef
- Kim S, Jung UJ, Kim SR. The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications. J Clin Med. 2025;14(2):386. PubMed, PubMedCentral, CrossRef
- Zhang X, Chen Z, Xiong Y, Zhou Q, Zhu LQ, Liu D. The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia. Neural Regen Res. 2025;20(2):402-415. PubMed, PubMedCentral, CrossRef
- Hernandez-Navarro I, Botana L, Diez-Mata J, Tesoro L, Jimenez-Guirado B, Gonzalez-Cucharero C, Alcharani N, Zamorano JL, Saura M, Zaragoza C. Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS. Int J Mol Sci. 2024;25(18):9890. PubMed, PubMedCentral, CrossRef
- Maccallini C, Budriesi R, De Filippis B, Amoroso R. Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity. Int J Mol Sci. 2024;25(15):8486. PubMed, PubMedCentral, CrossRef
- Simão S, Santos DF, Teixeira M, Agostinho RR, Rodrigues J, Vitorino M, Araújo IM. Unraveling the potential of gasotransmitters as neurogenic and neuroprotective molecules: focus on Alzheimer’s and Parkinson’s diseases. Redox Rep. 2026;31(1):2592413. PubMed, PubMedCentral, CrossRef
- Saini N, Singh D, Sandhir R. Bacopa monnieri prevents colchicine-induced dementia by anti-inflammatory action. Metab Brain Dis. 2019;34(2):505-518. PubMed, CrossRef
- Sil S, Ghosh T, Ghosh R. NMDA receptor is involved in neuroinflammation in intracerebroventricular colchicine-injected rats. J Immunotoxicol. 2016;13(4):474-489. PubMed, CrossRef
- Danukalo MV, Kolesnyk YM. Specificity of iNOS expression in the basal magnocellular nucleus of rats under early pathogenetic correction in experimental neurodestruction. Zaporozhye Med J. 2024;26(5):379-386. (In Ukrainian). CrossRef
- Guerra-Araiza C, Álvarez-Mejía AL, Sánchez-Torres S, Farfan-García E, Mondragón-Lozano R, Pinto-Almazán R, Salgado-Ceballos H. Effect of natural exogenous antioxidants on aging and on neurodegenerative diseases. Free Radic Res. 2013;47(6-7):451-462. PubMed, CrossRef
This work is licensed under a Creative Commons Attribution 4.0 International License.







