In this study, we used a model of a hemorrhagic stroke in a motor zone of the cortex in rats at the age of 3 months The report shows that cortical neurons can fuse with oligodendrocytes. In formed binuclear cells, the nucleus of an oligodendrocyte undergoes neuron specific reprogramming. It can be confirmed by changes in chromatin structure and in size of the second nucleus, by expression of specific neuronal markers and increasing total transcription rate. The nucleus of an oligodendrocyte likely transforms into a second neuronal nucleus. The number of binuclear neurons was validated with quantitative analysis. Fusion of neurons with oligodendrocytes might be a regenerative process in general and specifically following a stroke. The appearance of additional neuronal nuclei increases the functional outcome of the population of neurons. Participation of a certain number of binuclear cells in neuronal function might compensate for a functional deficit that arises from the death of a subset of neurons. After a stroke, the number of binuclear neurons increased in cortex around the lesion zone. In this case, the rate of recovery of stroke-damaged locomotor behavior also increased, which indicates the regenerative role of fusion. 1. Introduction Protection, rehabilitation, and stroke outcome are determined by the extent of the preserved neuronal tissue. Thus, the maintenance and regeneration of stroke-injured neurons is a prominent topic on which there are many publications, all of which represent neuronal regeneration exclusively as a result of neurogenesis. This tendency can be justified only in one case, when a stroke occurs in the dentate gyrus (fascia dentata hippocampus) or in the olfactory bulb. These two zones are reasonably considered neurogenic because they are sites of the replacement of granular neurons. Granular neurons are formed in two other neurogenic zones: the subgranular layer of the dentate gyrus [1–5] and the subventricular layer of the cerebral ventricles [6–8]. Neuroblasts migrate from these zones to the granular layer of the dentate gyrus [9–11] and to the olfactory bulbs [8, 12], where they differentiate into granular neurons. Reports of neurogenesis in other brain regions, as in the review of Gould [13], contradict other experiments [14–17]. Therefore, scientific consensus purports that, in other brain regions, neurogenesis does not occur. According to one hypothesis, neurogenesis does not normally occur in the cortex but appears after stroke [18, 19]. However, some publications do not confirm this point of view [20]. These issues
References
[1]
G. Kempermann, H. G. Kuhn, and F. H. Gage, “Genetic influence on neurogenesis in the dentate gyrus of adult mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 19, pp. 10409–10414, 1997.
[2]
G. Kempermann, H. G. Kuhn, and F. H. Gage, “More hippocampal neurons in adult mice living in an enriched environment,” Nature, vol. 386, no. 6624, pp. 493–495, 1997.
[3]
E. Gould, A. J. Reeves, M. Fallah, P. Tanapat, C. G. Gross, and E. Fuchs, “Hippocampal neurogenesis in adult old world primates,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 9, pp. 5263–5267, 1999.
[4]
D. R. Kornack and P. Rakic, “Continuation of neurogenesis in the hippocampus of the adult macaque monkey,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 10, pp. 5768–5773, 1999.
[5]
P. S. Eriksson, E. Perfilieva, T. Bj？rk-Eriksson et al., “Neurogenesis in the adult human hippocampus,” Nature Medicine, vol. 4, no. 11, pp. 1313–1317, 1998.
[6]
C. B. Johansson, S. Momma, D. L. Clarke, M. Risling, U. Lendahl, and J. Frisén, “Identification of a neural stem cell in the adult mammalian central nervous system,” Cell, vol. 96, no. 1, pp. 25–34, 1999.
[7]
F. Doetsch, I. Caille, D. A. Lim, J. M. Garcia-Verdugo, and A. Alvarez-Buylla, “Subventricular zone astrocytes are neural stem cells in the adult mammalian brain,” Cell, vol. 97, no. 6, pp. 703–716, 1999.
[8]
C. Lois and A. Alvarez-Buylla, “Long-distance neuronal migration in the adult mammalian brain,” Science, vol. 264, no. 5162, pp. 1145–1148, 1994.
[9]
C. Zhao, E. M. Teng, R. G. Summers Jr., G. L. Ming, and F. H. Gage, “Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus,” Journal of Neuroscience, vol. 26, no. 1, pp. 3–11, 2006.
[10]
N. Toni, D. A. Laplagne, C. Zhao et al., “Neurons born in the adult dentate gyrus form functional synapses with target cells,” Nature Neuroscience, vol. 11, no. 8, pp. 901–907, 2008.
[11]
N. Toni, E. M. Teng, E. A. Bushong et al., “Synapse formation on neurons born in the adult hippocampus,” Nature Neuroscience, vol. 10, no. 6, pp. 727–734, 2007.
[12]
M. A. Curtis, M. Kam, U. Nannmark et al., “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension,” Science, vol. 315, no. 5816, pp. 1243–1249, 2007.
[13]
E. Gould, “How widespread is adult neurogenesis in mammals?” Nature Reviews Neuroscience, vol. 8, no. 6, pp. 481–488, 2007.
[14]
J. B. Ackman, F. Siddiqi, R. S. Walikonis, and J. J. LoTurco, “Fusion of microglia with pyramidal neurons after retroviral infection,” Journal of Neuroscience, vol. 26, no. 44, pp. 11413–11422, 2006.
[15]
D. R. Kornack and P. Rakic, “Cell proliferation without neurogenesis in adult primate neocortex,” Science, vol. 294, no. 5549, pp. 2127–2130, 2001.
[16]
D. Koketsu, A. Mikami, Y. Miyamoto, and T. Hisatsune, “Nonrenewal of neurons in the cerebral neocortex of adult Macaque monkeys,” Journal of Neuroscience, vol. 23, no. 3, pp. 937–942, 2003.
[17]
K. L. Spalding, R. D. Bhardwaj, B. A. Buchholz, H. Druid, and J. Frisén, “Retrospective birth dating of cells in humans,” Cell, vol. 122, no. 1, pp. 133–143, 2005.
[18]
T. Nakagomi, A. Taguchi, Y. Fujimori et al., “Isolation and characterization of neural stem/progenitor cells from post-stroke cerebral cortex in mice,” The European Journal of Neuroscience, vol. 29, no. 9, pp. 1842–1852, 2009.
[19]
O. Saino, A. Taguchi, T. Nakagomi et al., “Immunodeficiency reduces neural stem/progenitor cell apoptosis and enhances neurogenesis in the cerebral cortex after stroke,” Journal of Neuroscience Research, vol. 88, no. 11, pp. 2385–2397, 2010.
[20]
R. J. Lichtenwalner and J. M. Parent, “Adult neurogenesis and the ischemic forebrain,” Journal of Cerebral Blood Flow and Metabolism, vol. 26, no. 1, pp. 1–20, 2006.
[21]
A. A. Paltsyn, E. G. Kolokol'chikova, N. B. Konstantinova, G. A. Romanova, F. M. Shakova, and A. A. Kubatiev, “Heterokaryon formation as a method for neuron regeneration in postischemic injury to cerebral cortex in rats,” Bulletin of Experimental Biology and Medicine, vol. 146, no. 4, pp. 485–488, 2008.
[22]
A. A. Paltsyn, N. B. Konstantinova, G. A. Romanova, F. M. Shakova, Y. N. Kvashennikova, and A. A. Kubatiev, “The role of cell fusion in physiological and reparative regeneration of the cerebral cortex,” Bulletin of Experimental Biology and Medicine, vol. 148, no. 5, pp. 825–831, 2009.
[23]
A. Kubatiev, A. Palcyn, N. Konstantinova, et al., “Cell fusion and reprogramming nuclei-mechanism of regeneration of brain cortex,” 6th International Congress of Pathophisiology, pp. 183–187, 2010.
[24]
B. D. Watson, W. D. Dietrich, and R. Busto, “Induction of reproducible brain infarction by photochemically initiated thrombosis,” Annals of Neurology, vol. 17, no. 5, pp. 497–504, 1985.
[25]
S. V. Komissarova, S. A. Turygyna, and V. V. Aleksandrin, “Model of inflammatory site in rat brain cortex,” Pathogenesis, vol. 9, no. 1, pp. 38–42, 2011 (Russian).
[26]
G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Elsevier, New York, NY, USA, 6th edition, 2007.
[27]
M. Alvarez-Dolado, R. Pardal, J. M. Garcia-Verdugo et al., “Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes,” Nature, vol. 425, no. 6961, pp. 968–973, 2003.
[28]
J. M. Weimann, C. A. Charlton, T. R. Brazelton, R. C. Hackman, and H. M. Blau, “Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 4, pp. 2088–2093, 2003.
[29]
J. M. Weimann, C. B. Johansson, A. Trejo, and H. M. Blau, “Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant,” Nature Cell Biology, vol. 5, no. 11, pp. 959–966, 2003.
[30]
J. Priller, D. A. Persons, F. F. Klett, G. Kempermann, G. W. Kreutzberg, and U. Dirnagl, “Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo,” Journal of Cell Biology, vol. 155, no. 5, pp. 733–738, 2001.
[31]
C. B. Johansson, S. Youssef, K. Koleckar et al., “Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation,” Nature Cell Biology, vol. 10, no. 5, pp. 575–583, 2008.
[32]
P. Rubin, D. M. Gash, J. T. Hansen, D. F. Nelson, and J. P. Williams, “Disruption of the blood-brain barrier as the primary effect of CNS irradiation,” Radiotherapy and Oncology, vol. 31, no. 1, pp. 51–60, 1994.
[33]
N. Davoust, C. Vuaillat, G. Androdias, and S. Nataf, “From bone marrow to microglia: barriers and avenues,” Trends in Immunology, vol. 29, no. 5, pp. 227–234, 2008.
[34]
A. Nishiyama, Z. Yang, and A. Butt, “Astrocytes and NG2-glia: what's in a name?” Journal of Anatomy, vol. 207, no. 6, pp. 687–693, 2005.
[35]
D. L. Montgomery, “Astrocytes: form, functions and role in disease,” Veterinary Pathology, vol. 3, no. 2, pp. 145–167, 1994.
[36]
A. Krawczyk and J. Jaworska-Adamu, “Synantocytes: the fifth type of glia? In comparison with astrocytes,” Folia Histochemica et Cytobiologica, vol. 48, no. 2, pp. 173–177, 2010.
[37]
A. M. Butt, J. Kiff, P. Hubbard, and M. Berry, “Synantocytes: new functions for novel NG2 expressing glia,” Journal of Neurocytology, vol. 31, no. 6-7, pp. 551–565, 2002.
[38]
M.-F. Guo, J. Z. Yu, and C.-G. Ma, “Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia,” Folia Neuropathologica, vol. 49, no. 2, pp. 78–87, 2011.
[39]
E. Morey-Holton, R. K. Globus, A. Kaplansky, and G. Durnova, “The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data,” Advances in Space Biology and Medicine, vol. 10, pp. 7–40, 2005.
[40]
N. B. Sviridkina, F. M. Shakova, C. V. Komissarova, I. P. Dubrovin, et al., “Morphofunctional study of antiortostatic hipokinesia action in the case of focal ischemic brain cortex damage,” Pathological Physiology and Experimental Therapy, no. 2, pp. 22–26, 2012.
