Effect of desynchronosis on oxidative stress biomarkers and the state of glial intermediate filaments in the brains of rats subject to aging

  • S. Kyrychenko Oles Honchar Dnipropetrovsk National University
  • N. Chernyshenko Oles Honchar Dnipropetrovsk National University
Keywords: constant lighting, lipid peroxidation, glutathione, aging, melatonin, glial fibrillary acidic protein, GFAP


Desynchronosis may be the cause of many diseases. Oxidative stress plays an important role in the pathogenesis of various diseases. The present study investigates the effect of constant light on biomarkers of oxidative stress and content of glial intermediate filaments protein in the brains of old rats. We found that desynchronosis led to development of oxidative stress in the hippocampus, cerebral cortex and cerebellum of old rats. Prolonged continuous lighting led to an increase in the content of TBA-reactive products in all studied regions of the brains of old rats. This indicates an activation of lipid peroxidation and oxidative stress. Significant changes in the content of TBA-reactive products were found in the departments responsible for the functions of the higher nervous activity, particularly in the hippocampus and cerebral cortex. The level of restored glutathione in all three regions of the brain decreased in the group of rats kept under constant illumination in comparison with the control group. The results of the indicators of locomotor and orienting-investigative activity of the animals in the "open field" test revealled changes in the indices for desynchronosis. This showed a reduction in locomotor activity, inhibition of exploratory activity and development of emotional stress. In the brains of old rats kept under constant illumination a significant increase in the content of glial fibrillary protein (GFAP) was shown. There was a significant increase in the intensity of the polypeptide zone 49 kDa in the filamentous and soluble fraction of the cerebellum and hippocampus. This fact indicates that desynchronosis activates fibrillogenesis in glial cells. At the same time, there is degradation of polypeptides GFAP with Mr in the field of 46 kDa. Melatonin is a universal adaptogen that regulates the function of many body systems. The amount of melatonin which is synthesized depends on the illumination mode. Violation of the global mode reduces the amount of melatonin and leads to the development of desynchronosis, which may be the cause of many diseases. The administration of melatonin helped reverse the changes – raising the level of restored glutathione and preventing the growth of the content of peroxidation products and indices of "open field" test, and also decreasing the degradation of GFAP and the amount of protein. The results indicate the protective effect of melatonin, showing reductions in glial reactivity and in the level of oxidative stress in the brains of old rats subject to desynchronosis. 


Baydas, G., Koz, S.T., Tuzcu, M., Etem, E., Nedzvetsky, V.S., 2007. Melatonin inhibits oxidative stress and apoptosis in fetal brains of hyperhomocysteinemic rat dams. J. Pineal Res. 43(3), 225–231. >> doi.org/10.1111/j.1600-079x.2007.00465.x

Bitto, A., Sell, C., Crowe, E., Lorenzini, A., Malaguti, M., Hrelia, S., Torres, C., 2010. Stress-induced senescence in human and rodent astrocytes. Exp. Cell Res. 316, 2961–2968. >> doi.org/10.1016/j.yexcr.2010.06.021

Calabrese, V., Lodi, R., Tonon, C., D’Agata, V., Sapienza, M., Scapagnini, G., Mangiameli, A., Pennisi, G., Stella, A.M., Butterfield, D.A., 2005. Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich’s ataxia. J. Neurol. Sci. 233, 145–162. >> doi.org/10.1016/j.jns.2005.03.012

Cherubini, A., Ruggiero, C., Morand, C., Lattanzio, F., Dell’aquila, G., Zuliani, G., Di Iorio, A., Andres-Lacueva, C., 2008. Dietary antioxidants as potential pharmacological agents for ischemic stroke. Curr. Med. Chem. 15, 1236–1248. >> doi.org/10.2174/092986708784310431

Cornelius, C., Crupi, R., Calabrese, V., Graziano, A., Milone, P., Pennisi, G., Radak, Z., Calabrese, E.J., Cuzzocrea, S., 2013. Traumatic brain injury: Oxidative stress and neuroprotection. Antioxid. Redox Signal. 19, 836–853. >> doi.org/10.1089/ars.2012.4981

Eng, L.F., Ghirnikar, R.S., Lee, Y.L., 2000. Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem. Res. 25, 1439–1451. >> doi.org/10.1023/a:1007677003387

Esposito, E., Cuzzocrea, S., 2010. Antiinflammatory activity of melatonin in central nervous system. Curr. Neuropharmacol. 8, 228–242. >> doi.org/10.2174/157015910792246155

Halliwell, B., 2006. Oxidative stress and neurodegeneration: Where are we now? J. Neurochem. 97, 1634–1658. >> doi.org/10.1111/j.1471-4159.2006.03907.x

Halliwell, B., 2012. Free radicals and antioxidants: Updating a personal view. Nutr. Rev. 70, 257–265. >> doi.org/10.1111/j.1753-4887.2012.00476.x

Lewén, A., 2001.Oxidative stress-dependent release of mitochondrial cytochrome c after traumatic brain injury. J. Cereb. Blood Flow Metab. 21, 914–920. >> doi.org/10.1097/00004647-200108000-00003

Michara, M., Uchiyama, M., Fukuzava, K., 1980. Thiobarbituric acid value on fresh homogenate of rat as a parameter of lipid peroxidation in aging, CCl4 intoxication, аnd vitamin E deficiency. Biochem. Med. 23(3), 302–311. >> doi.org/10.1016/0006-2944(80)90040-x

Miller, G.L., 1959. Protein determination for large numbers of samples. Anal. Chem. 31, 964–966. >> doi.org/10.1021/ac60149a611

Mistraletti, G., Umbrello, M., Sabbatini, G., Miori, S., Taverna, M., Cerri, B., Mantovani, E.S., Formenti, P., Spanu, P., D’Agostino, A., Salini, S., Morabito, A., Fraschini, F., Reiter, R.J., Iapichino, G., 2015. Melatonin reduces the need for sedation in ICU patients: A randomized controlled trial. Minerva Anestesiol. 81, 1298–1310.

Nazıroglu, M., 2011. TRPM2 cation channels, oxidative stress and neurological diseases: Where are we now? Neurochem. Res. 36, 355–366. >> doi.org/10.1007/s11064-010-0347-4

Nedzvetsky, V.S., Baydas, G., Nerush, P.A, Kirichenko, S.V., 2002. Melatonin is involved in regulation of the expression of neural cell adhesion molecules in the rat brain. Neurophysiology 34, 190–193. >> doi.org/10.1023/a:1020755300957

Pandi-Perumal, S.R., BaHammam, A.S., Brown, G.M., Spence, D.W., Bharti, V.K., Kaur, C., Hardeland, R., Cardinali, D.P., 2013. Melatonin antioxidative defense: Therapeutical implications for aging and neurodegenerative processes. Neurotox. Res. 23(3), 267–300. >> doi.org/10.1007/s12640-012-9337-4

Pekny, M., Wilhelmsson, U., Pekna, M., 2014. The dual role of astrocyte activation and reactive gliosis. Neurosci. Lett. 565, 30–38.

>> doi.org/10.1016/j.neulet.2013.12.071

Reiter, R.J., Guerrero, J.M., Escames, G., Pappolla, M.A., Acuña-Castroviejo, D., 1997. Prophylactic actions of melatonin in oxidative neurotoxicity. Ann. N. Y. Acad. Sci. 825, 70–78. >> doi.org/10.1111/j.1749-6632.1997.tb48415.x

Sedlak, J., Lindsay, R.H., 1968. Estimation of total, protein bound and non-protein sulfhydryl groups in tissue with Ellmann’s reagent. Anal. Biochem. 25, 192–205. >> doi.org/10.1016/0003-2697(68)90092-4

Senol, N., Nazıroglu, M., 2014. Melatonin reduces traumatic brain injury-induced oxidative stress in the cerebral cortex and blood of rats. Neural Regen. Res. 9(11), 1112–1116.

Vinod, C., Jagota, A., 2016. Daily NO rhythms in peripheral clocks in aging male Wistar rats: Protective effects of exogenous melatonin. Biogerontology 17: 859–871. >> doi.org/10.1007/s10522-016-9656-6

Yang, Y., Jiang, S., Dong, Y., Fan, C., Zhao, L., Yang, X., Li, J., Di, S., Yue, L., Liang, G., Reiter, R.J., Qu, Y., 2015. Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. J. Pineal Res. 58, 61–70. >> doi.org/10.1111/jpi.12193

Yatin, S.M., Varadarajan, S., Butterfield, D.A., 2000. Vitamin E prevents Alzheimer’s amyloid beta-peptide induced neuronal protein oxidation and reactive oxygen species production. J. Alzheimers Dis. 2(2), 123–131.

Zhao, L., An, R., Yang, Y., Yang, X., Liu, H., Yue, L., Li, X., Lin, Y., Reiter, R.J., Qu, Y., 2015. Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling. J. Pineal Res. 59(2), 230–239. >> doi.org/10.1111/jpi.12254