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Licensed Unlicensed Requires Authentication Published by De Gruyter April 20, 2021

Exposure to prolonged unpredictable light impairs spatial memory via induction of oxidative stress and tumor necrosis factor-alpha in rats

  • Oluwaseun S. Faborode ORCID logo EMAIL logo , Issa O. Yusuf , Paschal O. Okpe , Ann O. Okudaje and Samuel A. Onasanwo

Abstract

Objectives

The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats.

Methods

Artificial lighting was provided using an array of white light-emitting diodes coupled to a microcontroller that switches them on or off at unpredictable times and duration (light intensity = 200 ± 20 lx). Within the last eight days of 40 days exposure, animals were subjected to open field test, Morris water maze, and novel object recognition behavioral paradigms. Brain levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione S-transferase (GST), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were assayed.

Results

Exposed rats showed impaired spatial learning and memory (p<0.05), but no changes in object recognition memory or locomotor activity. Oxidative stress analyses also revealed significant changes in the concentrations of MDA, SOD, catalase, and GSH levels (p<0.05), not GST. Similarly, there was an increased TNF-α expression (p<0.05), not VEGF.

Conclusions

We conclude that oxidative stress is involved in memory impairment in rats exposed to prolonged unpredictable lights, which again suggests the detrimental effects of extended light exposure on the nervous system.


Corresponding author: Oluwaseun S. Faborode, Department of Human Physiology, College of Health Sciences, Bingham University, Karu, Nigeria; and Neuroscience and Oral Physiology Unit, Department of Physiology, University of Ibadan, Ibadan, Nigeria, Phone: +27747880949, +2348077467766, E-mail:

Acknowledgments

The authors would like to appreciate Aremu J.O and Okpanachi O.O of the Department of Computer Science and Human Physiology, Bingham University respectively, for their technical assistance.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Ethical approval: The local Institutional Review Board deemed the study exempt from review. All experimental procedures on rodents in the study were conducted following established protocols under the guidelines of the Principle of Laboratory Animal Care (National Institute of Health). At the time of the experimentation, the institution generally exempt studies with fewer animals from review. The study has indeed adhered to these guidelines as the number of animals was significantly reduced and refined that no invasive procedures were employed. Stress was significantly reduced, and no pain was inflicted throughout the experimentation.

References

1. Legates, TA, Fernandez, DC, Hattar, S. Light as a central modulator of circadian rhythms, sleep and affect. Nat Rev Neurosci 2014;15:443–54. https://doi.org/10.1038/nrn3743.Search in Google Scholar PubMed PubMed Central

2. Dibner, C, Schibler, U, Albrecht, U. The Mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol 2010;72:517–49. https://doi.org/10.1146/annurev-physiol-021909-135821.Search in Google Scholar PubMed

3. Ma, WP, Cao, J, Tian, M, Cui, MH, Han, HL, Yang, YX, et al.. Exposure to chronic constant light impairs spatial memory and influences long-term depression in rats. Neurosci Res 2007;59:224–30. https://doi.org/10.1016/j.neures.2007.06.1474.Search in Google Scholar PubMed

4. Lyons, LC, Rawashdeh, O, Katzoff, A, Susswein, AJ, Eskin, A. Circadian modulation of complex learning in diurnal and nocturnal Aplysia. Proc Natl Acad Sci U S A 2005;102:12589–94. https://doi.org/10.1073/pnas.0503847102.Search in Google Scholar PubMed PubMed Central

5. Medeiros, LN, Sanchez, TG. Tinnitus and cell phones: the role of electromagnetic radiofrequency radiation. Braz J Otorhinolaryngol 2016;82:97–104. https://doi.org/10.1016/j.bjorl.2015.04.013.Search in Google Scholar PubMed

6. Buckus, R, Strukčinskienė, B, Raistenskis, J, Stukas, R, Šidlauskienė, A, Čerkauskienė, R, et al.. A technical approach to the evaluation of radiofrequency radiation emissions from mobile telephony base stations. Int J Environ Res Publ Health 2017;14:244. https://doi.org/10.3390/ijerph14030244.Search in Google Scholar PubMed PubMed Central

7. Legates, TA, Altimus, CM, Wang, H, Lee, HK, Yang, S, Zhao, H, et al.. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 2012;491:594–8. https://doi.org/10.1038/nature11673.Search in Google Scholar PubMed PubMed Central

8. Huiberts, LM, Smolders, KCHJ, de Kort, YAW. Shining light on memory: effects of bright light on working memory performance. Behav Brain Res 2015;294:234–45. https://doi.org/10.1016/j.bbr.2015.07.045.Search in Google Scholar PubMed

9. Shan, LL, Guo, H, Song, NN, Jia, ZP, Hu, XT, Huang, JF, et al.. Light exposure before learning improves memory consolidation at night. Sci Rep 2015;5:15578. https://doi.org/10.1038/srep15578.Search in Google Scholar PubMed PubMed Central

10. Fujioka, A, Fujioka, T, Tsuruta, R, Izumi, T, Kasaoka, S, Maekawa, T. Effects of a constant light environment on hippocampal neurogenesis and memory in mice. Neurosci Lett 2011;488:41–4. https://doi.org/10.1016/j.neulet.2010.11.001.Search in Google Scholar PubMed

11. Tam, SKE, Hasan, S, Choi, HMC, Brown, LA, Jagannath, A, Hughes, S, et al.. Constant light desynchronizes olfactory versus object and visuospatial recognition memory performance. J Neurosci 2017;37:3555–67. https://doi.org/10.1523/jneurosci.3213-16.2017.Search in Google Scholar

12. Neto, SPD, Carneiro, BTS, Valentinuzzi, VS, Araújo, JF. Dissociation of the circadian rhythm of locomotor activity in a 22 h light-dark cycle impairs passive avoidance but not object recognition memory in rats. Physiol Behav 2008;94:523–7. https://doi.org/10.1016/j.physbeh.2008.03.013.Search in Google Scholar

13. Ruby, NF, Fernandez, F, Garrett, A, Klima, J, Zhang, P, Sapolsky, R, et al.. Spatial memory and long-term object recognition are impaired by circadian arrhythmia and restored by the GABAAAntagonist pentylenetetrazole. PLoS One 2013;8:e72433. https://doi.org/10.1371/journal.pone.0072433.Search in Google Scholar

14. NIH. Guide for the care and use of laboratory animals. Bethesda: NIH; 1996.Search in Google Scholar

15. Varghese, R, Majumdar, A, Kumar, G, Shukla, A. Rats exposed to 2.45 GHz of non-ionizing radiation exhibit behavioral changes with increased brain expression of apoptotic caspase 3. Pathophysiology 2018;25:19–30. https://doi.org/10.1016/j.pathophys.2017.11.001.Search in Google Scholar

16. Morris, R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47–60. https://doi.org/10.1016/0165-0270(84)90007-4.Search in Google Scholar

17. Dahle, LK, Hill, EG, Holman, RT. The thiobarbituric acid reaction and the autoxidations of polyunsaturated fatty acid methyl esters. Arch Biochem Biophys 1962;98:253–61. https://doi.org/10.1016/0003-9861(62)90181-9.Search in Google Scholar

18. Misra, HP, Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5. https://doi.org/10.1016/s0021-9258(19)45228-9.Search in Google Scholar

19. Sinha, AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389–94. https://doi.org/10.1016/0003-2697(72)90132-7.Search in Google Scholar

20. Habig, WH, Pabst, MJ, Jakoby, WB. Glutathione S transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9. https://doi.org/10.1016/s0021-9258(19)42083-8.Search in Google Scholar

21. Lowry, OH, Rosebrough, NJ, Farr, AL, Randall, RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75. https://doi.org/10.1016/s0021-9258(19)52451-6.Search in Google Scholar

22. D’Hooge, R, De Deyn, PP. Applications of the Morris water maze in the study of learning and memory. Brain Res Rev 2001;36:60–90.10.1016/S0165-0173(01)00067-4Search in Google Scholar

23. Hattar, S, Liao, HW, Takao, M, Berson, DM, Yau, KW. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 2002;295:1065–70. https://doi.org/10.1126/science.1069609.Search in Google Scholar PubMed PubMed Central

24. Hattar, S, Kumar, M, Park, A, Tong, P, Tung, J, Yau, KW, et al.. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol 2006;497:326–49. https://doi.org/10.1002/cne.20970.Search in Google Scholar PubMed PubMed Central

25. Krishnan, HC, Lyons, LC. Synchrony and desynchrony in circadian clocks: impacts on learning and memory. Learn Mem 2015;22:426–37. https://doi.org/10.1101/lm.038877.115.Search in Google Scholar PubMed PubMed Central

26. Kooijman, S, Van Den Berg, R, Ramkisoensing, A, Boon, MR, Kuipers, EN, Loef, M, et al.. Prolonged daily light exposure increases body fat mass through attenuation of brown adipose tissue activity. Proc Natl Acad Sci U S A 2015;112:6748–53. https://doi.org/10.1073/pnas.1504239112.Search in Google Scholar PubMed PubMed Central

27. Takuma, K, Hoshina, Y, Arai, S, Himeno, Y, Matsuo, A, Funatsu, Y, et al.. Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats. Neuroscience 2007;149:256–62. https://doi.org/10.1016/j.neuroscience.2007.07.042.Search in Google Scholar PubMed

28. Bangasser, DA, Shors, TJ. Acute stress impairs trace eyeblink conditioning in females without altering the unconditioned response. Neurobiol Learn Mem 2004;82:57–60. https://doi.org/10.1016/j.nlm.2004.03.001.Search in Google Scholar PubMed PubMed Central

29. Whissell, PD, Eng, D, Lecker, I, Martin, LJ, Wang, D-S, Orser, BA. Acutely increasing δGABAA receptor activity impairs memory and inhibits synaptic plasticity in the hippocampus. Front Neural Circ 2013;7:146. https://doi.org/10.3389/fncir.2013.00146.Search in Google Scholar PubMed PubMed Central

30. Miedel, CJ, Patton, JM, Miedel, AN, Miedel, ES, Levenson, JM. Assessment of spontaneous alternation, novel object recognition and limb clasping in transgenic mouse models of Amyloid-β; and tau neuropathology. J Vis Exp 2017. https://doi.org/10.3791/55523.Search in Google Scholar PubMed PubMed Central

31. Ettcheto, M, Sánchez-López, E, Pons, L, Busquets, O, Olloquequi, J, Beas-Zarate, C, et al.. Dexibuprofen prevents neurodegeneration and cognitive decline in APPswe/PS1dE9 through multiple signaling pathways. Redox Biol 2017;13:345–52. https://doi.org/10.1016/j.redox.2017.06.003.Search in Google Scholar PubMed PubMed Central

32. Lucassen, PJ, Meerlo, P, Naylor, AS, van Dam, AM, Dayer, AG, Fuchs, E, et al.. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: implications for depression and antidepressant action. Eur Neuropsychopharmacol 2010;20:1–17. https://doi.org/10.1016/j.euroneuro.2009.08.003.Search in Google Scholar PubMed

33. Jin, X, Wu, L, Zheng, H, Mishima, S. Retinal light damage: I. The influences of light intensity and exposure duration at moderate and low intensities of cyclic light. Yan Ke Xue Bao 1998;14:215–9.Search in Google Scholar

34. Rasheed, N, Ahmad, A, Al-Sheeha, M, Alghasham, A, Palit, G. Neuroprotective and anti-stress effect of A68930 in acute and chronic unpredictable stress model in rats. Neurosci Lett 2011;504:151–5. https://doi.org/10.1016/j.neulet.2011.09.021.Search in Google Scholar PubMed

35. Akbaraly, NT, Hininger-Favier, I, Carrière, I, Arnaud, J, Gourlet, V, Roussel, AM, et al.. Plasma selenium over time and cognitive decline in the elderly. Epidemiology 2007;18:52–8. https://doi.org/10.1097/01.ede.0000248202.83695.4e.Search in Google Scholar PubMed

36. Costantini, D, Monaghan, P, Metcalfe, NB. Loss of integration is associated with reduced resistance to oxidative stress. J Exp Biol 2013;216:2213–20. https://doi.org/10.1242/jeb.083154.Search in Google Scholar PubMed

37. Adhikari, M, Arora, R. The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity. Environ Toxicol 2016;31:641–54. https://doi.org/10.1002/tox.22076.Search in Google Scholar PubMed

38. El-Bakry, HA, Ismail, IA, Soliman, SS. Immunosenescence-like state is accelerated by constant light exposure and counteracted by melatonin or turmeric administration through DJ-1/Nrf2 and P53/Bax pathways. J Photochem Photobiol B Biol 2018;186:69–80. https://doi.org/10.1016/j.jphotobiol.2018.07.003.Search in Google Scholar PubMed

39. Baksheeva, VE, Tiulina, VV, Tikhomirova, NK, Gancharova, OS, Komarov, SV, Philippov, PP, et al.. Suppression of light-induced oxidative stress in the retina by mitochondria-targeted antioxidant. Antioxidants. 2019;8:3.10.3390/antiox8010003Search in Google Scholar PubMed PubMed Central

40. Sultana, R, Butterfield, DA. Oxidatively modified GST and MRP1 in Alzheimer’s disease brain: implications for accumulation of reactive lipid peroxidation products. Neurochem Res 2004;29:2215–20. https://doi.org/10.1007/s11064-004-7028-0.Search in Google Scholar PubMed

41. Yuan, CY, Lee, YJ, Hsu, GSW. Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats. J Biomed Sci 2012;19:51. https://doi.org/10.1186/1423-0127-19-51.Search in Google Scholar PubMed PubMed Central

42. Nehru, B, Anand, P. Oxidative damage following chronic aluminium exposure in adult and pup rat brains. J Trace Elem Med Biol 2005;19:203–8. https://doi.org/10.1016/j.jtemb.2005.09.004.Search in Google Scholar PubMed

43. McCracken, E, Valeriani, V, Simpson, C, Jover, T, McCulloch, J, Dewar, D. The lipid peroxidation by-product 4-hydroxynonenal is toxic to axons and oligodendrocytes. J Cereb Blood Flow Metab 2000;20:1529–36. https://doi.org/10.1097/00004647-200011000-00002.Search in Google Scholar

44. Halliwell, B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–58. https://doi.org/10.1111/j.1471-4159.2006.03907.x.Search in Google Scholar

45. Castanon-Cervantes, O, Wu, M, Ehlen, JC, Paul, K, Gamble, KL, Johnson, RL, et al.. Dysregulation of inflammatory responses by chronic circadian disruption. J Immunol 2010;185:5796–805. https://doi.org/10.4049/jimmunol.1001026.Search in Google Scholar

46. Schulze-Osthoff, K, Bakker, AC, Vanhaesebroeck, B, Beyaert, R, Jacob, WA, Fiers, W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 1992;267:5317–23. https://doi.org/10.1016/s0021-9258(18)42768-8.Search in Google Scholar

47. Pober, JS, Min, W, Bradley, JR. Mechanisms of endothelial dysfunction, injury, and death. Annu Rev Pathol Mech Dis 2009;4:71–95. https://doi.org/10.1146/annurev.pathol.4.110807.092155.Search in Google Scholar

48. Fiore, M, Angelucci, F, Alleva, E, Branchi, I, Probert, L, Aloe, L. Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNF-alpha. Behav Brain Res 2000;112:165–75. https://doi.org/10.1016/s0166-4328(00)00180-7.Search in Google Scholar

49. Xiao, Z, Liu, Q, Mao, F, Wu, J, Lei, T. TNF-α-induced VEGF and MMP-9 expression promotes hemorrhagic transformation in pituitary adenomas. Int J Mol Sci 2011;12:4165–79. https://doi.org/10.3390/ijms12064165.Search in Google Scholar

50. Maloney, JP, Gao, L. Proinflammatory cytokines increase vascular endothelial growth factor expression in alveolar epithelial cells. Mediat Inflamm 2015;2015:1–7. https://doi.org/10.1155/2015/387842.Search in Google Scholar

51. Castilla, MÁ, Caramelo, C, Gazapo, RM, Martín, O, González-Pacheco, FR, Tejedor, A, et al.. Role of vascular endothelial growth factor (VEGF) in endothelial cell protection against cytotoxic agents. Life Sci 2000;67:1003–13. https://doi.org/10.1016/s0024-3205(00)00693-7.Search in Google Scholar

52. Arroyo, MVA, Caramelo, C, Castilla, MA, Pacheco, FRG, Martin, O, Arias, J. Role of vascular endothelial growth factor in the response to vessel injury. Kidney Int Suppl 1998;54:S7–9.10.1046/j.1523-1755.1998.06804.xSearch in Google Scholar PubMed

53. Storkebaum, E, Lambrechts, D, Carmeliet, P. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. BioEssays 2004;26:943–54. https://doi.org/10.1002/bies.20092.Search in Google Scholar PubMed

54. Cao, L, Jiao, X, Zuzga, DS, Liu, Y, Fong, DM, Young, D, et al.. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 2004;36:827–35. https://doi.org/10.1038/ng1395.Search in Google Scholar PubMed

Received: 2020-07-04
Accepted: 2021-01-23
Published Online: 2021-04-20

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