The Subventricular Zone Is Able to Respond to a Demyelinating Lesion After Localized Radiation

Abstract

Radiation is a common tool in the treatment of brain tumors that induces neurological deficits as a side effect. Some of these deficits appear to be related to the impact of radiation on the neurogenic niches, producing a drastic decrease in the proliferative capacity of these regions. In the adult mammalian brain, the subventricular zone (SVZ) of the lateral ventricles is the main neurogenic niche. Neural stem/precursor cells (NSCs) within the SVZ play an important role in brain repair following injuries. However, the irradiated NSCs' ability to respond to damage has not been previously elucidated. In this study, we evaluated the effects of localized radiation on the SVZ ability to respond to a lysolecithin-induced demyelination of the striatum. We demonstrated that the proliferation rate of the irradiated SVZ was increased after brain damage and that residual NSCs were reactivated. The irradiated SVZ had an expansion of doublecortin positive cells that appeared to migrate from the lateral ventricles toward the demyelinated striatum, where newly generated oligodendrocytes were found. In addition, in the absence of demyelinating damage, remaining cells in the irradiated SVZ appeared to repopulate the neurogenic niche a year post-radiation. These findings support the hypothesis that NSCs are radioresistant and can respond to a brain injury, recovering the neurogenic niche. A more complete understanding of the effects that localized radiation has on the SVZ may lead to improvement of the current protocols used in the radiotherapy of cancer.

Generation of reactive astrocytes from NG2 cells is regulated by sonic hedgehog

“…This indicates that without gene manipulation, NG21/DCX1 cells are not able to acquire the phenotype of mature neurons, which is in accordance with a study showing a massive appearance of DCX1 cells 3 days after cortical injury, but their complete disappearance 28 days after injury (Susarla et al, 2014). Moreover, it was shown that Dcx is also expressed in NG2 cells (Plane et al, 2012) and in the progenitors that give rise to oligodendrocytes in the subvetricular zone (Capilla-Gonzalez et al, 2014); therefore, we suppose that Dcx is not a specific marker of neuronal progenitor.…”

The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging

“…Hence, the neurogenic system of aged mice becomes a better model for comparisons with adult human beings than the neurogenic system from young rodents. The maintained oligodendrogenesis provides new insight into the relevance of the oligodendrocytes throughout life, which could be a response to myelin damaged during aging (Nait-Oumesmar et al, 1999; Jablonska et al, 2010; Gonzalez-Perez and Alvarez-Buylla, 2011; Capilla-Gonzalez et al, in press). Moreover, oligodendrogenesis could be beneficial for the proper function of the remaining neurons in the aged brain.…”

“…Neuroblasts in the RMS retain their ability to proliferate (Smith and Luskin, 1998; Poon et al, 2010), but once they reach the OB, neuroblasts begin radial migration and mature into interneurons that integrate in preexisting functional circuits (Lois and Alvarez-Buylla, 1994; Luskin et al, 1997; Carleton et al, 2003; Imayoshi et al, 2008; Kelsch et al, 2010; Lazarini and Lledo, 2011). Although most SVZ precursor cells generate neuroblasts to support OB neurogenesis, a small subpopulation of precursors gives rise to cells in the oligodendroglial lineage, which are able to migrate toward the corpus callosum, striatum, or septum to differentiate into myelinating oligodendrocytes (Nait-Oumesmar et al, 1999; Menn et al, 2006; Gonzalez-Perez et al, 2009; Gonzalez-Perez and Alvarez-Buylla, 2011; Capilla-Gonzalez et al, in press). …”

The aged brain: genesis and fate of residual progenitor cells in the subventricular zone

“…Then, neuroblasts move radially and mature into interneurons that integrate in preexisting functional circuits (Lois and Alvarez-Buylla, 1994 ; Lois et al, 1996 ; Luskin et al, 1997 ; Carleton et al, 2003 ; Alvarez-Buylla and Lim, 2004 ; Imayoshi et al, 2008 ; Kelsch et al, 2010 ; Lazarini and Lledo, 2011 ). In rodents, most SVZ precursor cells become neuroblasts to support OB neurogenesis, while a small subpopulation of new cells migrates to periventricular areas such as the corpus callosum or striatum, where they give rise to myelinating oligodendrocytes, both in the normal brain and after demyelinating lesion (Nait-Oumesmar et al, 1999 ; Menn et al, 2006 ; Gonzalez-Perez et al, 2009 ; Capilla-Gonzalez et al, 2014b ).…”