The expression of Bcl-2 protein in pyramidal neurons in hippocampal fields CA1, CA2, CA3, and CA4 was studied in Mongolian gerbils (Meriones unguiculatus) in the early (two days) and late (seven days) reperfusion periods after 7-min ischemia of the forebrain, after use of ischemic postconditioning (IPostC) and in sham-operated animals (n = 60). The highest level of Bcl-2 expression in the latter group was seen in neurons in field CA4 and the lowest in neurons in field CA1 (p < 0.01). Reversible ischemic injury led to an increase in the deficit of morphologically unaltered neurons in the hippocampus at the later period of reperfusion and a significant decrease in neuronal Bcl-2 expression at the early reperfusion period, this decrease being significantly smaller in the late reperfusion period. IPostC consisting of three episodes of reperfusion-ischemia (15/15 sec) promoted a significant increase in the number of morphologically unaltered neurons in fields CA1 and CA3 in the early reperfusion period. An increase in the level of Bcl-2 expression was seen in the cytoplasm of morphologically unaltered neurons in all hippocampal fields. In the late reperfusion period after IPostC, the number of unaltered neurons was increased in fields CA1, CA3, and CA4 (p < 0.05); only hippocampal field CA1 neurons showed a significant increase in Bcl-2 expression (by 12.7%, p < 0.01). These results lead to the conclusion that the cytoporotective effect of IPostC for hippocampal field CA1 is mediated by a mechanism leading to an increase in Bcl-2 expression, i.e., via blockade of apoptosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
O. V. Vetrovoi, E. A. Rybnikova, T. S. Glushchenko, and M. O. Samoilov, “Effects of hypoxic postconditioning on expression of the antiapoptotic protein Bcl-1 and the neurotrophin BDNF in hippocampal field CA1 in rats subjected to severe hypoxia,” Morfologiya, 145, No. 2, 16–20 (2014).
N. S. Shcherbak, M. M. Galagudza, A. N. Kuz’menkov, et al., “Morpho functional changes in hippocampal field CA1 in Mongolian gerbils on use of ischemic postconditioning,” Morfologiya, 142, No. 5, 12–16 (2012).
Y. J. Cao, T. Shibata, and N. G. Rainov, “Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model,” Gene Ther., 9, No. 6, 415–419 (2002).
E. Castren, Y. Ohga, M. P. Berzaghi, et al., “bcl-2 messenger RNA is localized in neurons of the developing and adult rat brain,” Neuroscience, 61, 165–177 (1994).
Z. M. Ding, B. Wu, W. Q. Zhang, et al., “Neuroprotective effects of ischemic preconditioning and postconditioning on global brain ischemia in rats through the same effect on inhibition of apoptosis,” Int. J. Mol. Sci., 13, No. 5, 6089–6101 (2012).
A. Hara, M. Niwa, M. Nakashima, et al., “Protective effect of apoptosis-inhibitory agent, N-tosyl-L-phenylalanyl chloromethyl ketone against ischemia-induced hippocampal neuronal damage,” J. Cereb. Blood Flow Metab., 18, No. 8, 819–823 (1998).
D. J. Kane, T. Ord, R. Anton, and D. E. Bredesen, “Expression of bcl-2 inhibits necrotic neural cell death,” J. Neurosci. Res., 40, 269–275 (1995).
M. Kiessling, G. Stumm, Y. Xie, et al., “Differential transcription and translation of immediate early genes in the gerbil hippocampus after transient global ischemia,” J. Cereb. Blood Flow Metab., 13, 914–924 (1993).
T. Kirino, “Delayed neuronal death in the gerbil hippocampus following ischemia,” Brain Res., 239, 57–69 (1982).
M. S. Lawrence, J. R. McLaughlin, G. H. Sun, et al., “Herpes simplex viral vectors expressing Bcl-2 are neuroprotective when delivered after a stroke,” J. Cereb. Blood Flow Metab., 17, No. 7, 740–744 (1997).
W. J. Loskota, P. Lomax, and M. A. Verity, A Stereotaxic Atlas of the Mongolian Gerbil Brain, Ann Arbor Science Publishers, Ann Arbor, USA (1974).
J. C. Martinou, M. Dubois-Dauphin, J. K. Staple, et al., “Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia,” Neuron, 13, No. 1, 17–30 (1994).
D. E. Merry, D. J. Veis, W. F. Hickey, and S. J. Korsmeyer, “Bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS,” Development, 120, No. 2, 301–311 (1994).
M. Nemethova, V. Danielisova, M. Gottlieb, et al., “Ischemic postconditioning in the rat hippocampus: mapping of proteins involved in reversal of delayed neuronal death,” Arch. Ital. Biol., 148, No. 1, 23–32 (2010).
L. Radenovic, V. Selakovic, B. Janac, and P. R. Andjus, “Neuroprotective efficiency of NMDA receptor blockade in the striatum and CA3 hippocampus after various durations of cerebral ischemia in gerbils,” Acta Physiol. Hung., 98, No. 1, 32–44 (2011).
K. Shimazaki, A. Ishida, and N. Kawai, “Increase in bcl-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbil hippocampus,” Neurosci. Res., 20, No. 1, 95–99 (1994).
W. Stummer, K. Weber, B. Tranmer, et al., “Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia,” Stroke, 25, 1862–1869 (1994).
B. Xing, H. Chen, M. Zhang, et al., “Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion injury in the rat,” Stroke, 39, No. 8, 2362–2369 (2008).
Q. G. Zhang, R. M. Wang, D. Han, et al., “Preconditioning neuroprotection in global cerebral ischemia involves NMDA receptor-mediated ERK-JNK3 crosstalk,” Neurosci. Res., 63, No. 3, 205–212 (2009).
H. Zhao, C. Ren, X. Chen, and J. Shen, “From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia,” Curr. Drug Targets, 13, 173–187 (2012).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Morfologiya, Vol. 148, No. 5, pp. 21–27, September–October, 2015.
Rights and permissions
About this article
Cite this article
Shcherbak, N.S., Rusakova, A.G., Galagudza, M.M. et al. Changes in the Expression of Bcl-2 Protein in Neurons in the Hippocampal Fields after Use of Ischemic Postconditioning of the Brain. Neurosci Behav Physi 46, 833–838 (2016). https://doi.org/10.1007/s11055-016-0318-6
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-016-0318-6