Abstract
The antiapoptotic protein Bcl-xL is associated with several neuroplastic processes such as formation of synapses, regulation of spontaneous and evoked synaptic responses, and release of neurotransmitters. Dependence of expression on activity of neurons is characteristic for many proteins participating in regulation of neuroplasticity. Whether such property is exhibited by the Bcl-xL protein was analyzed using in vivo optogenetic stimulation of hippocampal glutamatergic neurons expressing channelrhodopsin ChR2H134 under CAMKIIa promoter in the adeno-associated viral vector, followed by immunohistochemical determination of the level of Bcl-xL protein in these neurons and surrounding cells. Increase in the level of early response c-Fos protein following illumination with blue light was indicative of activation of these hippocampal neurons. The optogenetic activation of hippocampus resulted in a significant increase in the level of antiapoptotic protein Bcl-xL in the photosensitive neurons as well as in the surrounding cells. The dependence of the level of expression of Bcl-xL protein on the activity of neurons indicates that this protein possesses one more important property that is essential for participation in neuroplastic processes in the brain.
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Abbreviations
- AAV:
-
adeno-associated viruses
- ChR2 or ChR2H134:
-
short and full designation of channelrhodopsin-2, respectively
- PBS:
-
phosphate buffered saline
- PBST:
-
PBS containing 0.1% Triton X-100
- YFP and EGFP:
-
yellow and enhanced green fluorescent proteins, respectively
References
Jonas, E. (2006) Bcl-xL regulates synaptic plasticity, Mol. Interv., 6, 208–222.
Gal, A., Pentelenyi, K., Remenyi, V., Wappler, E. A., Safrany, G., Skopal, J., and Nagy, Z. (2009) Bcl-2 or BclxL gene therapy increases neural plasticity proteins nestin and c-fos expression in PC12 cells, Neurochem. Int., 55, 349–353.
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., and Jonas, E. A. (2008) Bcl-xL induces Drp1-dependent synapse formation in cultured hippocampal neurons, Proc. Natl. Acad. Sci. USA, 105, 2169–2174.
Li, H., Alavian, K. N., Lazrove, E., Mehta, N., Jones, A., Zhang, P., Licznerski, P., Graham, M., Uo, T., Guo, J., Rahner, C., Duman, R. S., Morrison, R. S., and Jonas, E. A. (2013) A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis, Nat. Cell. Biol., 15, 773–785.
Yassin, L., Benedetti, B. L., Jouhanneau, J. S., Wen, J. A., Poulet, J. F., and Barth, A. L. (2010) An embedded subnetwork of highly active neurons in the neocortex, Neuron, 68, 1043–1050.
Peter, M., Bathellier, B., Fontinha, B., Pliota, P., Haubensak, W., and Rumpel, S. (2013) Transgenic mouse models enabling photolabeling of individual neurons in vivo, PLoS One, 8, e62132.
Lanshakov, D. A., Sukhareva, E. V., Kalinina, T. S., and Dygalo, N. N. (2016) Dexamethasone-induced acute excitotoxic cell death in the developing brain, Neurobiol. Dis., 91, 1–9.
Formentini, L., Pereira, M. P., Sanchez-Cenizo, L., Santacatterina, F., Lucas, J. J., Navarro, C., MartinezSerrano, A., and Cuezva, J. M. (2014) In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning, EMBO J., 33, 762–778.
Du, J., McEwen, B., and Manji, H. K. (2009) Glucocorticoid receptors modulate mitochondrial function: a novel mechanism for neuroprotection, Commun. Integr. Biol., 2, 350–352.
Du, J., Wang, Y., Hunter, R., Wei, Y., Blumenthal, R., Falke, C., Khairova, R., Zhou, R., Yuan, P., MachadoVieira, R., McEwen, B. S., and Manji, H. K. (2009) Dynamic regulation of mitochondrial function by glucocorticoids, Proc. Natl. Acad. Sci. USA, 106, 3543–3548.
McClure, C., Cole, K. L., Wulff, P., Klugmann, M., and Murray, A. J. (2011) Production and titering of recombinant adeno-associated viral vectors, J. Vis. Exp., 27, e3348.
Shishkina, G. T., Kalinina, T. S., and Dygalo, N. N. (2004) Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood, Neuroscience, 129, 521–528.
Dygalo, N. N., Kalinina, T. S., and Shishkina, G. T. (2008) Neonatal programming of rat behavior by downregulation of alpha2A-adrenoreceptor gene expression in the brain, Ann. N. Y. Acad. Sci., 1148, 409–414.
Ramirez, S., Liu, X., MacDonald, C. J., Moffa, A., Zhou, J., Redondo, R. L., and Tonegawa, S. (2015) Activating positive memory engrams suppresses depression-like behavior, Nature, 522, 335–339.
Lanshakov, D. A., Drozd, U. S., Zapara, T. A., and Dygalo, N. N. (2016) Transfer of optogenetic vectors into the brain of neonatal animals to study neuron functions during subsequent periods of development, Vavilov J. Genet. Breed., 20, 255–261.
Shishkina, G. T., Kalinina, T. S., Berezova, I. V., Bulygina, V. V., and Dygalo, N. N. (2010) Resistance to the development of stress-induced behavioral despair in the forced swim test associated with elevated hippocampal Bcl-xl expression, Behav. Brain Res., 213, 218–224.
Dygalo, N. N., Kalinina, T. S., Bulygina, V. V., and Shishkina, G. T. (2012) Increased expression of the antiapoptotic protein Bcl-xL in the brain is associated with resilience to stress-induced depression-like behavior, Cell. Mol. Neurobiol., 32, 767–776.
Shishkina, G. T., Kalinina, T. S., Berezova, I. V., and Dygalo, N. N. (2012) Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated with fluoxetine: correlations with serotonin metabolism and depressive-like behavior, Neuropharmacology, 62, 177–183.
Shishkina, G. T., Kalinina, T. S., Bulygina, V. V., Lanshakov, D. A., Babluk, E. V., and Dygalo, N. N. (2015) Anti-apoptotic protein Bcl-xL expression in the midbrain raphe region is sensitive to stress and glucocorticoids, PLoS One, 10, e0143978.
Tye, K. M., and Deisseroth, K. (2012) Optogenetic investigation of neural circuits underlying brain disease in animal models, Nat. Rev. Neurosci., 13, 251–266.
Kawashima, T., Okuno, H., and Bito, H. (2014) A new era for functional labeling of neurons: activity-dependent promoters have come of age, Front. Neural. Circuits, 23, doi: 10.3389/fncir.2014.00037.
Cohen, S., and Greenberg, M. E. (2008) Communication between the synapse and the nucleus in neuronal development, plasticity, and disease, Annu. Rev. Cell. Dev. Biol., 24, 183–209.
De la Fuente, V., Federman, N., Zalcman, G., Salles, A., Freudenthal, R., and Romano, A. (2015) NF-κB transcription factor role in consolidation and reconsolidation of persistent memories, Front. Mol. Neurosci., 9, doi: 10.3389/fnmol.2015.00050.
Grillot, D. A., Gonzalez-Garcia, M., Ekhterae, D., Duan, L., Inohara, N., Ohta, S., Seldin, M. F., and Nunez, G. (1997) Genomic organization, promoter region analysis, and chromosome localization of the mouse bcl-x gene, J. Immunol., 158, 4750–4757.
Grad, J. M., Zeng, X. R., and Boise, L. H. (2000) Regulation of Bcl-xL: a little bit of this and a little bit of STAT, Curr. Opin. Oncol., 12, 543–549.
Schipke, C. G., and Kettenmann, H. (2004) Astrocyte responses to neuronal activity, Glia, 47, 226–232.
Croft, W., Dobson, K. L., and Bellamy, T. C. (2015) Plasticity of neuron-glial transmission: equipping glia for long-term integration of network activity, Neural Plast., doi: 10.1155/2015/765792.
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Original Russian Text © D. A. Lanshakov, U. S. Drozd, N. N. Dygalo, 2017, published in Biokhimiya, 2017, Vol. 82, No. 3, pp. 481-486.
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Lanshakov, D.A., Drozd, U.S. & Dygalo, N.N. Optogenetic stimulation increases level of antiapoptotic protein Bcl-xL in Neurons. Biochemistry Moscow 82, 340–344 (2017). https://doi.org/10.1134/S0006297917030129
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DOI: https://doi.org/10.1134/S0006297917030129