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k252a Inhibits H2S-Alleviated Homocysteine-Induced Cognitive Dysfunction in Rats

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Abstract

Homocysteine (Hcy) is a neurotoxicity amino acid that causes cognitive dysfunction. Hydrogen sulfide (H2S) is a neuroprotective gas molecular and can improve cognitive ability in a range of physiological concentrations. Our previous study confirmed that H2S (by its donor, NaHS) ameliorates cognitive impairment in Hcy-exposed rats, but the underlying mechanism has not been well elucidated. Accumulating evidence suggests that k252a, the furanosylated indolocarbazoleas, is usually used as the receptor tyrosine kinase B (TrkB) antagonist and blocks brain-derived neurotrophic factor (BDNF)/TrkB signaling, thus leading to cognitive decline. Interestingly, we previously demonstrated that k252a reversed H2S alleviated Hcy-induced endoplasmic reticulum stress and neuronal apoptosis via inhibiting BDNF-TrkB pathway. Therefore, we assumed that k252a might inhibit the protective effect of H2S on Hcy-induced cognitive dysfunction. We used Hcy to establish a rat model of cognitive impairment. We found that after administration of k252a by intracerebroventricular injection, the beneficial effect of H2S on Hcy-induced cognitive decline is abolished, as reflected by the increasing escape latency and time spent in the target quadrant in the Morris Water Maze (MWM) test as well as decreased spontaneous alternation in Y-maze test and the lower discrimination index in the Novel Object Recognition (NOR) test in rats co-treated with sodium hydrosulfide (NaHS, a donor of H2S), Hcy and k252a. Our findings suggested that k252a antagonized the effect of H2S on preventing Hcy-related cognitive decline. Our finding expands the understanding of the potential mechanism on the resistant role of H2S in Hcy-caused cognitive damage.

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REFERENCES

  1. Reddy, V.S., Trinath, J., and Reddy, G.B., Biochimie, 2019, vol. 165, pp. 19–31.

    Article  CAS  PubMed  Google Scholar 

  2. Bhatia, P. and Singh, N., Fundam. Clin. Pharmacol., 2015, vol. 29, no. 6, pp. 522–528.

    Article  CAS  PubMed  Google Scholar 

  3. Lin, L. and Du, H., Spectrochim. Acta A, Mol. Biomol. Spectrosc., 2018, vol. 202, pp. 314–318.

    Article  CAS  Google Scholar 

  4. Kumar, A., Palfrey, H.A., Pathak, R., Kadowitz, P.J., Gettys, T.W. and Murthy, S.N., Nutr. Metab. (Lond.), 2017, vol. 14, p. 78.

    Article  CAS  Google Scholar 

  5. Rizzo, A. and Sciorsci, R.L., Res. Vet. Sci., 2019, vol. 122, pp. 29–35.

    Article  CAS  PubMed  Google Scholar 

  6. Ma, F., Wu, T., Zhao, J., Ji, L., Song, A., Zhang, M., and Huang, G., Nutrients, 2017, vol. 9, no. 7.

  7. Kovalska, M., Tothova, B., Kovalska, L., Tatarkova, Z., Kalenska, D., Tomascova, A., Adamkov, M., and Lehotsky, J., Neurochem. Res., 2018, vol. 43, no. 9, pp. 1766–1778.

    Article  CAS  PubMed  Google Scholar 

  8. Shan, H., Qiu, J., Chang, P., Chu, Y., Gao, C., Wang, H., Chen, G., Luo, C., Wang, T., Chen, X., Zhang, M., and Tao, L., Front. Cell. Neurosci., 2019, vol. 13, p. 349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hu, L.F., Lu, M., Hon Wong, P.T., and Bian, J.S., Antioxid. Redox Signal., 2011, vol. 15, no. 2, pp. 405–419.

    Article  CAS  PubMed  Google Scholar 

  10. Kumar, M. and Sandhir, R., CNS Neurol. Disord. Drug Targets., 2018, vol. 17, no. 9, pp. 654–670.

    Article  CAS  PubMed  Google Scholar 

  11. Wang, J.F., Li, Y., Song, J.N., and Pang, H.G., Neurochem. Int., 2014, vol. 64, pp. 37–47.

    Article  CAS  PubMed  Google Scholar 

  12. Li, M.H., Tang, J.P., Zhang, P., Li, X., Wang, C.Y., Wei, H.J., Yang, X.F., Zou, W., and Tang, X.Q., Behav. Brain Res., 2014, vol. 262, pp. 35–41.

    Article  CAS  PubMed  Google Scholar 

  13. Li, M., Zhang, P., Wei, H.J., Li, M.H., Zou, W., Li, X., Gu, H.F., and Tang, X.Q., Int. J. Neuropsychopharmacol., 2017, vol. 20, no. 4, pp. 305–315.

    Article  CAS  PubMed  Google Scholar 

  14. Berdun, S., Rychter, J., and Vergara, P., Am. J. Physiol. Gastrointest. Liver Physiol., 2015, vol. 309, no. 10, pp. G801– G806.

    Article  CAS  PubMed  Google Scholar 

  15. Coltella, N., Manara, M.C., Cerisano, V., Trusolino, L., Di Renzo, M.F., Scotlandi, K., and Ferracini, R., FASEB J., 2003, vol. 17, no. 9, pp. 1162–1164.

    Article  CAS  PubMed  Google Scholar 

  16. Garcia, L., Castillo, C., Carballo, J., Rodriguez, Y., Forsyth, P., Medina, R., Martinez, J.C., and Longart, M., Neuroscience, 2013, vol. 236, pp. 88–98.

    Article  CAS  PubMed  Google Scholar 

  17. Xu, J., Yu, L., Minobe, E., Lu, L., Lei, M., and Kameyama, M., Am. J. Physiol. Cell Physiol., 2016, vol. 310, no. 2, pp. C136– C141.

    Article  PubMed  Google Scholar 

  18. Nakagomi, A., Okada, S., Yokoyama, M., Yoshida, Y., Shimizu, I., Miki, T., Kobayashi, Y., and Minamino, T., NPJ Aging Mech. Dis., 2015, vol. 1, p. 15009.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Bernard-Gauthier, V., Boudjemeline, M., Rosa-Neto, P., Thiel, A., and Schirrmacher, R., Bioorg. Med. Chem., 2013, vol. 21, no. 24, pp. 7816–7829.

    Article  CAS  PubMed  Google Scholar 

  20. Ginsberg, S.D., Malek-Ahmadi, M.H., Alldred, M.J., Chen, Y., Chen, K., Chao, M.V., Counts, S.E., and Mufson, E.J., Neurobiol. Dis., 2019, p. 104540.

  21. Solinas, S.M.G., Edelmann, E., Lessmann, V., and Migliore, M., PLoS Comput. Biol., 2019, vol. 15, no. 4, p. e1006975.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Park, H.L., Kim, S.W., Kim, J.H., and Park, C.K., Dis. Model. Mech., 2019, vol. 12, no. 6.

  23. Luo, H., Xiang, Y., Qu, X., Liu, H., Liu, C., Li, G., Han, L., and Qin, X., Front. Pharmacol., 2019, vol. 10, p. 395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Luo, L., Liu, X.L., Mu, R.H., Wu, Y.J., Liu, B.B., Geng, D., Liu, Q., and Yi, L.T., Brain Res. Bull., 2015, vol. 114, pp. 62–69.

    Article  CAS  PubMed  Google Scholar 

  25. JiaWen, W., Hong, S., ShengXiang, X., and Jing, L., Clin. Exp. Dermatol., 2018, vol. 43, no. 3, pp. 254–261.

    Article  CAS  PubMed  Google Scholar 

  26. Wei, L., Kan, L.Y., Zeng, H.Y., Tang, Y.Y., Huang, H.L., Xie, M., Zou, W., Wang, C.Y., Zhang, P., and Tang, X.Q., Neuromolecular Med., 2018, vol. 20, no. 2, pp. 252–261.

    Article  CAS  PubMed  Google Scholar 

  27. Liang, Y., Yu, Y.H., Yu, H.J., and Ma, L.S., Eur. Rev. Med. Pharmacol. Sci., 2019, vol. 23, no. 9, pp. 3561–3568.

    CAS  PubMed  Google Scholar 

  28. Sawamoto, A., Okuyama, S., Nakajima, M., and Furukawa, Y., Pharmacol. Rep., 2019, vol. 71, no. 4, pp. 653–658.

    Article  CAS  PubMed  Google Scholar 

  29. Wei, H.J., Xu, J.H., Li, M.H., Tang, J.P., Zou, W., Zhang, P., Wang, L., Wang, C.Y., and Tang, X.Q., Acta Pharmacol. Sin., 2014, vol. 35, no. 6, pp. 707–715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kumar, M. and Sandhir, R., Nitric Oxide, 2019, vol. 90, pp. 15–28.

    Article  CAS  PubMed  Google Scholar 

  31. Liu, H.Y., Wei, H.J., Wu, L., Liu, S.M., Tang, Y.Y., Zou, W., Wang, C.Y., Zhang, P., and Tang, X.Q., Clin. Exp. Pharmacol. Physiol., 2020, vol. 47, no. 2, pp. 302–312.

    Article  CAS  PubMed  Google Scholar 

  32. Zhao, J., Zhang, Y., Liu, Y., Tang, W.Q., Ji, C.H., Gu, J.H., and Jiang, B., Neurosci. Lett., 2021, vol. 742, p. 135535.

    Article  CAS  PubMed  Google Scholar 

  33. Ma, F., Lv, X., Du, Y., Chen, H., Liu, S., Zhao, J., Gao, Y., An, P., Zhou, X., Song, A., Sun, C., Wang, G., Ji, Y., Wang, X., Xu, W., and Huang, G., Dement. Geriatr. Cogn. Disord., 2019, pp. 1–12.

  34. Lv, X., Zhou, D., Ge, B., Chen, H., Du, Y., Liu, S., Ji, Y., Sun, C., Wang, G., Gao, Y., Li, W., and Huang, G., J. Alzheimer’s Dis., 2019, vol. 70, no. 4, pp. 1133–1142.

    Article  CAS  Google Scholar 

  35. Di, Meco A., Li, J.G., Barrero, C., Merali, S., and Pratico, D., Mol. Psychiatry, 2018.

  36. Moretti, R. and Caruso, P., Int. J. Mol. Sci., 2019, vol. 20, no. 1.

  37. Nagpure, B.V. and Bian, J.S., Handb. Exp. Pharmacol., 2015, vol. 230, pp. 193–215.

    Article  CAS  PubMed  Google Scholar 

  38. Vandini, E., Ottani, A., Zaffe, D., Calevro, A., Canalini, F., Cavallini, G.M., Rossi, R., Guarini, S., and Giuliani, D., Pharmacology, 2019, vol. 103, nos. 1–2, pp. 50–60.

    Article  CAS  PubMed  Google Scholar 

  39. Tang, Y.Y., Wang, A.P., Wei, H.J., Li, M.H., Zou, W., Li, X., Wang, C.Y., Zhang, P., and Tang, X.Q., Behav. Brain Res., 2018, vol. 342, pp. 35–42.

    Article  CAS  PubMed  Google Scholar 

  40. Wang, Q., Chen, R., Zhang, C., Inam, U.L., Piao, F., and Shi, X., Mol. Cell Biochem., 2019, vol. 457, nos. 1–2, pp. 133–143.

    Article  CAS  PubMed  Google Scholar 

  41. Choi, S.H., Kim, H.J., Cho, H.J., Park, S.D., Lee, N.E., Hwang, S.H., Cho, I.H., Hwang, H., Rhim, H., Kim, H.C., and Nah, S.Y., Mol. Neurobiol., 2019, vol. 56, no. 5, pp. 3280–3294.

    Article  CAS  PubMed  Google Scholar 

  42. Iulita, M.F., Bistue Millon, M.B., Pentz, R., Aguilar, L.F., Do Carmo, S., Allard, S., Michalski, B., Wilson, E.N., Ducatenzeiler, A., Bruno, M.A., Fahnestock, M., and Cuello, A.C., Neurobiol. Dis., 2017, vol. 108, pp. 307–323.

    Article  CAS  PubMed  Google Scholar 

  43. Fletcher, J.L., Murray, S.S., and Xiao, J., Int. J. Mol. Sci., 2018, vol. 19, no. 12.

  44. Li, S., Cai, J., Feng, Z.B., Jin, Z.R., Liu, B.H., Zhao, H.Y., Jing, H.B., Wei, T.J., Yang, G.N., Liu, L.Y., Cui, Y.J., and Xing, G.G., Neurochem. Res., 2017, vol. 42, no. 10, pp. 2712–2729.

    Article  CAS  PubMed  Google Scholar 

  45. Li, J., Ding, X., Zhang, R., Jiang, W., Sun, X., Xia, Z., Wang, X., Wu, E., Zhang, Y., and Hu, Y., Neuroscience, 2015, vol. 303, pp. 103–114.

    Article  CAS  PubMed  Google Scholar 

  46. Li, X., Chen, C., Yang, X., Wang, J., Zhao, M.L., Sun, H., Zhang, S., and Tu, Y., Evid. Based Complement. Alternat. Med., 2017, vol. 2017, p. 8460145.

    PubMed  PubMed Central  Google Scholar 

  47. Wu, J., Dong, L., Zhang, M., Jia, M., Zhang, G., Qiu, L., Ji, M., and Yang, J., Neurochem. Res., 2013, vol. 38, no. 11, pp. 2440–2449.

    Article  CAS  PubMed  Google Scholar 

  48. Hu, M., Zou, W., Wang, C.Y., Chen, X., Tan, H.Y., Zeng, H.Y., Zhang, P., Gu, H.F., and Tang, X.Q., Oxid. Med. Cell. Longev., 2016, vol. 2016, p. 2153745.

    PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the General Scientific Research Project of Hunan Provincial Department of Education (19C0650), Natural Science Foundation of China (81771178), and the Natural Science Youth Foundation of Hunan Province (2020JJ5147).

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    Authors and Affiliations

    1. Department of Neurology, Nanhua Affiliated Hospital, University of South China, 336 E Dongfeng Road, 421001, Hengyang, Hunan, P. R. China

      Juan He, Min Li, Man-Hong Li, Wei Zou & Ping Zhang

    2. Institute of Neuroscience, Hengyang Medical College, University of South China, 421001, Hengyang, Hunan, P. R. China

      Juan He, Min Li, Wei Zou & Ping Zhang

    3. Hunan University of Environment and Biology, 421001, Hengyang, Hunan, P. R. China

      Hai-Jun Wei

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    Ethical approval. All procedures performed in studies involving rats were in accordance with the ethical standards of the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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    He, J., Wei, HJ., Li, M. et al. k252a Inhibits H2S-Alleviated Homocysteine-Induced Cognitive Dysfunction in Rats. Neurochem. J. 15, 308–316 (2021). https://doi.org/10.1134/S1819712421030053

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