DOI: https://doi.org/10.22263/2312-4156.2026.2.55
T.V. Klimut1, A.V. Zaerko1, S.M. Zimatkin1, S.V. Emelyanchik2
C-fos in the brain piriform cortex neurons of rats in cholestasis
1Grodno State Medical University, Grodno, Republic of Belarus
2Grodno State University named after Yanka Kupala, Grodno, Republic of Belarus
Vestnik VGMU. 2026;25(2):55-61.
Abstract.
Cholestasis (bile stasis) is known as a severe complication of many liver and biliary tract diseases. It disrupts bile flow from the liver into the duodenum, leading to digestive problems (especially lipid disturbances) and excessive bile components (bilirubin, bile acids, cholesterol) entering the bloodstream and then the brain. This disrupts the brain structure and function.
Objectives. To elucidate the molecular mechanisms underlying these disorders, particularly the involvement of the c-fos protein in the adaptation of neurons in the piriform cortex to cholestasis.
Material and Methods. The study involved neurons in layers II and III of the piriform cortex of rats at 2, 5, 10, 20, 45, and 90 days after common bile duct (CBD) ligation/transection or sham surgery (control). Histological, immunohistochemical, morphometric, and statistical methods were used.
Results. In cholestasis, an increase in the number of c-fos-positive neurons with high immunoreactivity was observed in layer II of the piriform cortex. Peak activation occurred on day 2, with an increased number of neurons with high immunoreactivity persisting on days 5, 10, and 20. These values returned to control values on days 45 and 90. In layer III of the piriform cortex, no significant differences were found between the control and experimental groups at any time point.
Conclusions. Cholestasis causes an early increase in c fos protein expression in neurons of the 2nd layer of the piriform cortex of the rat brain, stimulating the functional activity and adaptation of neurons to this pathological effect. When cholestasis is eliminated, the expression of c fos in them normalizes. In neurons of the 3rd layer, which is highly resistant to cholestasis, the expression of c fos does not change, which indicates the unequal involvement of this protein in the mechanisms of adaptation of neurons of different layers of the piriform cortex.
Keywords: cholestasis, rat piriform cortex, neurons, c-fos.
References
1. Yuldasheva GB. The prevalence of yeast disease and modern treatment methods. Re-health Journal. 2022;(1):42-50. (In Russ.).
2. Zimatkin SM, Emelyanchik SV. Neurons in the brain with bile circulation disorders: monografiya. Grodno, RB: GrGMU; 2021. 368 р. (In Russ.).
3. Ochoa-Lantigua P, Moreira-Mendoza Jh, García Ríos CA, Rodas JA, Leon-Rojas JE. The little known ribbon shaped piriform cortex: a key node in temporal lobe epilepsy – anatomical insights and its potential for surgical treatment. Diagnostics. 2024 Dec;14(24):2838. doi: http://dx.doi.org/10.3390/diagnostics14242838
4. Klimut TV, Zaerko AV, Emelyanchik SV, Zimatkin SM. Sternal cortex neurons' resistance to cholesterol. Zhurnal Grodnenskogo Gosudarstvennogo Meditsinskogo Universiteta. 2025;23(6):601-609. (In Rus.). doi: http://dx.doi.org/10.25298/2221-8785-2025-23-6-601-609
5. Aparicio SYL, Fierro ÁJL, Abreu GEA, Cárdenas RT, Hernández LIG, Ávila GAC, et al. Current opinion on the use of c-Fos in neuroscience. NeuroSci. 2022 Dec;3(4):687-702. doi: http://dx.doi.org/10.3390/neurosci3040050
6. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Official Journal of the European Union. 2010;276:33-79.
7. Grigoryev IP, Korzhevskiy DE. Modern biological material fixation technologies used in immunohistochemical studies (overview). Sovremennye Tekhnologii v Meditsine. 2018;10(2):156-165. (In Russ.).
8. Korzhevskiy DE, Kirik OV, Petrova ES, Karpenko MN, Grigoryev IP, Sukhorukova EG, i dr; Korzhevskiy DE, red. Theoretical foundations and practical application of immunohistochemistry: rukovodstvo. 2-e izd, ispr i dop. Saint Petersburg, RF: SpetsLit; 2014. 119 р. (In Russ.).
9. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. London: Academic Press; 2007. 448 p.
10. Omelchenko VP, Demidova AA. Informatics, medical informatics, statistics. Moscow, RF: GEOTAR-Media; 2021. 608 р. (In Russ.).
11. Abramov AV, Shamenko VA, Kolesnik YuM. Expression of c-Fos protein in rat hypothalamus with multiday action of intermittent hypoxic hypoxia. Aktual'nі Problemi Suchasnoї Meditsini Vіsnik Ukraїns'koї Medichnoї Stomatologіchnoї Akademії. 2017;17(4-2):5-8. (In Russ.).
12. Babrowicz B, Xing B, Jensen F. Early life seizures differentially activate c-Fos in hippocampal CA1 cell populations. The Premier Journal for Undergraduate Publications in the Neurosciences. 2021:1-10.
13. Úbeda-Contreras J, Marín-Blasco I, Nadal R, Armario A. Brain c-fos expression patterns induced by emotional stressors differing in nature and intensity. Brain Structure and Function. 2018 Jun;223(5):2213-2227. doi: http://dx.doi.org/10.1007/s00429-018-1624-2
14. Babaei P, Faraji N, Eyvani K. c-Fos expression differentially acts in the healthy brain compared with Alzheimer’s disease. Gene Expression. 2025;24(3):209-218. doi: http://dx.doi.org/10.14218/GE.2024.00080
15. Russo MJ, Franks KM, Oghaz R, Axel R, Siegelbaum SA. Synaptic organization of anterior olfactory nucleus inputs to piriform cortex. Journal of Neuroscience. 2020 Dec;40(49):9414-9425. doi: http://dx.doi.org/10.1523/JNEUROSCI.0965-20.2020
16. Recatalá M, Hidalgo P, Nàcher J, Blasco-Ibáñez JM, Crespo C, Varea E. Ondansetron blocks fluoxetine effects in immature neurons in the adult rat piriform cortex layer II. Neuroscience Letters. 2025 Jan:847:138099. doi: http://dx.doi.org/10.1016/j.neulet.2024.138099
17. Rubio A, Belles M, Belenguer G, Vidueira S, Fariñas I, Nacher J. Characterization and isolation of immature neurons of the adult mouse piriform cortex. Developmental Neurobiology. 2016 Jul;76(7):748-763. doi: http://dx.doi.org/10.1002/dneu.22357
18. Vadodaria KC, Yanpallewar SU, Vadhvani M, Toshniwal D, Liles LC, Rommelfanger KS, et al. Noradrenergic regulation of plasticity marker expression in the adult rodent piriform cortex. Neuroscience Letters. 2017 Mar:644:76-82. doi: http://dx.doi.org/10.1016/j.neulet.2017.02.060
Submitted 05.02.2026
Accepted 14.04.2026
Information about authors:
Tatyana V. Klimut – postgraduate of the Chair of Histology, Cytology & Embryology, Grodno State Medical University, https://orcid.org/0009-0001-5670-9030, e-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра.;
A.V. Zaerko – Candidate of Biological Sciences, associate professor of the Chair of Histology, Cytology & Embryology, Grodno State Medical University, https://orcid.org/0000-0001-6155-040X
S.M. Zimatkin – Doctor of Biological Sciences, professor, head of the Chair of Histology, Cytology & Embryology, Grodno State Medical University, https://orcid.org/0000-0001-5728-2588
S.V. Emelyanchik – Doctor of Biological Sciences, associate professor, head of the Chair of Ecology, Grodno State University named after Yanka Kupala, https://orcid.org/0009-0009-3032-8203
