A reduced expression of Bcl-xL in the hippocampus is accompanied by a depression-like phenotype in rats
- 作者: Shishkina G.T.1, Lanshakov D.A.1, Bannova A.V.1, Komysheva N.P.1, Dygalo N.N.1
-
隶属关系:
- The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
- 期: 卷 41, 编号 3 (2024)
- 页面: 231-239
- 栏目: Experimental Articles
- URL: https://cardiosomatics.orscience.ru/1027-8133/article/view/653887
- DOI: https://doi.org/10.31857/S1027813324030024
- EDN: https://elibrary.ru/EQVQHW
- ID: 653887
如何引用文章
详细
The previously identified ability of the anti-apoptotic protein Bcl-xL to increase expression in the hippocampus in response to stress, which correlated with resistance to stress-induced depression (Shishkina et al., 2010; Dygalo et al., 2012), indicates the potential use of this protein as a target for reducing symptoms of depressive disorder. The aim of this work was to evaluate in rats the effect of suppression of Bcl-xL expression in the hippocampus (using a TET-ON system based on lentiviral vectors for doxycycline-controlled transgene expression) on behavior in the forced swim test. The detected decrease in the expression (determined by immunoblotting) of Bcl-xL in the hippocampus and less pronounced in the frontal cortex was accompanied by a clear depressive-like effect, manifested by a shorter latency period before the first episode of freezing and a longer duration of passive behavior. Animals that received joint administration of the vector and doxycycline also showed a significant increase in the expression of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, the relative weight of the adrenal glands, and a decrease in the stress level of corticosterone in the blood plasma compared to groups that received separate administrations of these drugs. Relative adrenal weights were significantly negatively correlated with Bcl-xL expression levels in the frontal cortex. Overall, gene-directed reduction of Bcl-xL expression in the hippocampus resulted in a depressive-like response in the forced swim test in rats. This behavioral effect was accompanied by a change in the functioning of the adrenal glands, manifested by an increase in the weight of the glands and a decrease in the stress level of corticosterone in the peripheral circulation.
全文:

作者简介
G. Shishkina
The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
编辑信件的主要联系方式.
Email: gtshi@bionet.nsc.ru
俄罗斯联邦, Novosibirsk
D. Lanshakov
The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Email: gtshi@bionet.nsc.ru
俄罗斯联邦, Novosibirsk
A. Bannova
The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Email: gtshi@bionet.nsc.ru
俄罗斯联邦, Novosibirsk
N. Komysheva
The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Email: gtshi@bionet.nsc.ru
俄罗斯联邦, Novosibirsk
N. Dygalo
The Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Email: gtshi@bionet.nsc.ru
俄罗斯联邦, Novosibirsk
参考
- Dygalo N.N., Kalinina T.S., Bulygina V.V., Shishkina G.T. // Cell. Mol. Neurobiol. 2012. V. 32. P. 767–776.
- McEwen B.S. // Metabolism. 2005. V. 54. P. 20–23.
- Lucassen P.J., Pruessner J., Sousa N., Almeida O.F., Van Dam A.M., Rajkowska G., Swaab D.F., Czéh B. // Acta Neuropathol. 2014. V. 127. P. 109–135.
- Nestler E.J., Russo S.J. // Neuron. 2024. V. 112(12). P. 1911–1929.
- Lucassen P.J., Vollmann-Honsdorf G.K., Gleisberg M., Czéh B., De Kloet E.R., Fuchs E. // Eur. J. Neurosci. 2001. V. 14(1). P. 161–166.
- Lucassen P.J., Heine V.M., Muller M.B., van der Beek E.M., Wiegant V.M., De Kloet E.R., Joels M., Fuchs E., Swaab D.F., Czeh B. // CNS Neurol. Disord. Drug Targets. 2006. V. 5. P. 531–546.
- Kubera M., Obuchowicz E., Goehler L., Brzeszcz J., Maes M. // Prog Neuropsychopharmacol. Biol. Psychiatry. 2011. V. 35. P. 744–759.
- Culig L., Surget A., Bourdey M., Khemissi W., Le Guisquet A.M., Vogel E., Sahay A., Hen R., Belzung C. // Neuropharmacology. 2017. V. 126. P. 179–189.
- Planchez B., Surget A., Belzung C. // Curr. Opin. Pharmacol. 2020. V. 50. P. 88–95.
- Jones K.L., Zhou M., Jhaveri D.J. // NPJ Sci. Learn. 2022. V. 7. P. 16.
- Murray F., Hutson P.H. // Eur. J. Pharmacol. 2007. V. 569. P. 41–47.
- Kosten T.A., Galloway M.P., Duman R.S., Russell D.S., D’Sa C. // Neuropsychopharmacology. 2008. V. 33. P. 545–558.
- Shishkina G.T., Kalinina T.S., Berezova I.V., Bulygina V.V., Dygalo N.N. // Behav. Brain Res. 2010. V. 213. P. 218–224.
- Malkesman O., Austin D.R., Tragon T., Henter I.D., Reed J.C., Pellecchia M., Chen G., Manji H.K. // Mol. Psychiatry. 2012. V. 17. P. 770–780.
- Wang Y., Xiao Z., Liu X., Berk M. // Hum. Psychopharmacol. 2011. V. 26(2). P. 95–101.
- Shishkina G.T., Kalinina T.S., Berezova I.V., Dygalo N.N. // Neuropharmacology. 2012. V. 62. P. 177–183.
- Engel D., Zomkowski A.D., Lieberknecht V., Rodrigues A.L., Gabilan N.H. // J. Psychiatr. Res. 2013. V. 47. P. 802–808.
- Dygalo N.N., Bannova A.V., Sukhareva E.V., Shishkina G.T., Ayriyants K.A., Kalinina T.S. // Biochemistry (Mosc). 2017. V. 82. P. 345–350.
- De-Paula V.J., Dos Santos C.C.C., Luque M.C.A., Ali T.M., Kalil J.E., Forlenza O.V., Cunha-Neto E. // Metab. Brain Dis. 2021. V. 36. P. 193–197.
- González-García M., García I., Ding L., O’Shea S., Boise L.H., Thompson C.B., Núñez G. // Proc. Natl. Acad. Sci. USA. 1995. V. 92. P. 4304–4308.
- Jonas E.A., Porter G.A., Alavian K.N. // Front. Physiol. 2014. V. 5. P. 355.
- Szulc J., Wiznerowicz M., Sauvain M.O., Trono D., Aebischer P. // Nat. Methods. 2006. V. 3. P. 109–116.
- Porsolt R.D., Le Pichon M., Jalfre M. // Nature. 1977. V. 266. P. 730–732.
- Porsolt R.D., Anton G., Blavet N., Jalfre M. // Eur. J. Pharmacol. 1978. V. 47. P. 379–391.
- Bannova A.V., Menshanov P.N., Dygalo N.N. // Neurochem. J. 2019. V. 13. P. 344–348.
- Castagné V., Porsolt R.D., Moser P. // Eur. J. Pharmacol. 2009. V. 616. P. 128–133.
- Ge C., Wang S., Wu X., Lei L. // Behav. Brain Res. 2024. V. 465. P. 114934.
- Nakamura A., Swahari V., Plestant C., Smith I., McCoy E., Smith S., Moy S.S., Anton E.S., Deshmukh M. // J. Neurosci. 2016. V. 36. P. 5448–5461.
- Ma K., Zhang Z., Chang R., Cheng H., Mu C., Zhao T., Chen L., Zhang C., Luo Q., Lin J., Zhu Y., Chen Q. // Cell Death Differ. 2020. V. 27. P. 1036–1051.
- Cui W., Chen C., Gong L., Wen J., Yang S., Zheng M., Gao B., You J., Lin X., Hao Y., Chen Z., Wu Z., Gao L., Tang J., Yuan Z., Sun X., Jing L., Wen G. // CNS Neurosci. Ther. 2024. V. 30. P. e14377.
- Li M., Wang D., He J., Chen L., Li H. // Pharmacol Res. 2020. V. 151. P. 104547.
- Park H.A., Licznerski P., Alavian K.N., Shanabrough M., Jonas E.A. // Antioxid. Redox Signal. 2015. V. 22. P. 93–108.
- Jansen J., Scott M., Amjad E., Stumpf A., Lackey K.H., Caldwell K.A., Park H.A. // Biology (Basel). 2021. V. 10. P. 772.
- Jonas E.A., Hoit D., Hickman J.A., Brandt T.A., Polster B.M., Fannjiang Y., McCarthy E., Montanez M.K., Hardwick J.M., Kaczmarek L.K. // J. Neurosci. 2003. V. 23. P. 8423–8431.
- Li H., Chen Y., Jones A.F., Sanger R.H., Collis L.P., Flannery R., McNay E.C., Yu T., Schwarzenbacher R., Bossy B., Bossy-Wetzel E., Bennett M.V., Pypaert M., Hickman J.A., Smith P.J., Hardwick J.M., Jonas E.A. // Proc. Natl. Acad. Sci. USA. 2008. V. 105. P. 2169–2174.
- Bas J., Nguyen T., Gillet G. // Int. J. Mol. Sci. 2021. V. 22. P. 3202.
- Stone E.A., Lin Y. // Eur. J. Pharmacol. 2008. V. 580. P. 135–142.
- Noguchi T., Makino S., Matsumoto R., Nakayama S., Nishiyama M., Terada Y., Hashimoto K. // Endocrinology. 2010. V. 151. P. 4344–4355.
- Caudal D., Jay T.M., Godsil B.P. // Front. Behav. Neurosci. 2014. V. 8. P. 19.
- Karandrea D., Kittas C., Kitraki E. // Neuroendocrinology. 2002. V. 75. P. 217–226.
- Shishkina G.T., Bulygina V.V., Dygalo N.N. // Psychopharmacology (Berl). 2015. V. 232. P. 51–60.
- Gascoyne D.M., Kypta R.M., Vivanco d. M. // J. Biol. Chem. 2003. V. 278. P. 18022–18029.
- Viegas L.R., Vicent G.P., Barañao J.L., Beato M., Pecci A. // J. Biol. Chem. 2004. V. 279. P. 9831–9839.
- Du J., McEwen B., Manji H.K. // Commun. Integr. Biol. 2009. V. 2(4). P. 350–352.
- Drakulić D., Veličković N., Stanojlović M., Grković I., Mitrović N., Lavrnja I., Horvat A. // J. Neuroendocrinol. 2013. V. 25. P. 605–616.
- Khan M., Baussan Y., Hebert-Chatelain E. // Biomolecules. 2023. V. 13. P. 695.
- Chakrapani S., Eskander N., De Los Santos L.A., Omisore B.A., Mostafa J.A. // Cureus. 2020. V. 12. P. e11396.
- Duman R.S., Monteggia L.M. // Biol. Psychiatry. 2006. V. 59(12). P. 1116–1127.
- Stepanichev M., Dygalo N.N., Grigoryan G., Shishkina G.T., Gulyaeva N. // Biomed. Res. Int. 2014. V. 2014. P. 932757.
- Stepanichev M., Manolova A., Peregud D., Onufriev M., Freiman S., Aniol V., Moiseeva Y., Novikova M., Lazareva N., Gulyaeva N. // Neuroscience. 2018. V. 375. P. 49–61.
- Gulyaeva N.V. // Biochemistry (Mosc). 2023. V. 88. P. 565–589.
- Schaaf M.J., De Kloet E.R., Vreugdenhil E. // Stress. 2000. V. 3. P. 201–208.
- Chao C.C., Ma Y.L., Lee E.H. // Brain Pathol. 2011. V. 21. P. 150–162.
- Kim Y.K., Na K.S., Myint A.M., Leonard B.E. // Prog. Neuropsychopharmacol. Biol. Psychiatry. 2016. V. 64. P. 277–284.
- Martianova E., Aniol V.A., Manolova A.O., Kvichansky A.A., Gulyaeva N.V. // Acta Histochem. 2019. V. 121. P. 368–375.
- Serrats J., Grigoleit J.S., Alvarez-Salas E., Sawchenko P.E. // Brain Behav. Immun. 2017. V. 62. P. 53–63.
- Min X., Wang G., Cui Y., Meng P., Hu X., Liu S., Wang Y. // Front. Immunol. 2023. V. 14. P. 1110775.
补充文件
