Striatal astrocytes produce neuroblasts in an excitotoxic model of Huntington's disease

Abstract

In the adult brain, subsets of astrocytic cells residing in well-defined neurogenic niches constitutively generate neurons throughout life. Brain lesions can stimulate neurogenesis in otherwise non-neurogenic regions, but whether local astrocytic cells generate neurons in these conditions is unresolved. Here, through genetic and viral lineage tracing in mice, we demonstrate that striatal astrocytes become neurogenic following an acute excitotoxic lesion. Similar to astrocytes of adult germinal niches, these activated parenchymal progenitors express nestin and generate neurons through the formation of transit amplifying progenitors. These results shed new light on the neurogenic potential of the adult brain parenchyma.

Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions

“…But we and others have recently found that parenchymal astrocytes residing in the striatum can also generate neurons (Magnusson et al, 2014;Nato et al, 2015;Luzzati et al, 2014;Duan et al, 2015;Shen et al, 2015). These striatal astrocytes are triggered by certain injuries, such as stroke, to activate latent neurogenic properties and produce neurons in a burst of proliferation (Fig.…”

“…3). As mentioned, the similarities between parenchymal astrocytes and neural stem cells even extend to an intrinsic capacity of parenchymal astrocytes to generate neurons, at least when it comes to striatal astrocytes in vivo (Magnusson et al, 2014;Nato et al, 2015;Duan et al, 2015;Luzzati et al, 2014) and cortical astrocytes when isolated and cultured in vitro (Buffo et al, 2008;Shimada et al, 2012;Sirko et al, 2013). But the relatedness between the two cell types might go even further than that.…”

“…Even so, the finding soon afterwards that adult humans also have ongoing neurogenesis in the striatum came unexpectedly (Ernst et al, 2014). Mice, which are the most widely used laboratory animals, do not normally exhibit striatal neurogenesis under physiological conditions (Teramoto et al, 2003;Yamashita et al, 2006;Magnusson et al, 2014;Nato et al, 2015), except during a short period after birth (Inta et al, 2008). However, there is no reason to assume that the human brain should be more similar to the mouse brain than to that of other mammals.…”

“…Although this ability is dormant, it can be brought out by stimulating the cells with growth factors in vitro (Buffo et al, 2008;Sirko et al, 2013;Shimada et al, 2012). Recently, it has been shown that some parenchymal astrocytes in the striatum can, after certain injuries, also produce neurons in vivo (Magnusson et al, 2014;Nato et al, 2015). The neurons generated in this way are, however, few and it is not known whether they can contribute to functional recovery in a meaningful way.…”

The function of NFIX during developmental and adult neurogenesis

“…Its deletion might be sufficient to convert a substantial number of adult hippocampal neuroblasts to become oligodendrocytes without the concurrent cell death that occurs upon Nfix deletion. There is precedent for similar cell-type conversions between disparate cell types, for example it was recently shown that adult striatal astrocytes exhibit a latent neurogenic program that is actively suppressed via Notch signalling (Magnusson et al, 2014) and elicited by injury (Nato et al, 2015).…”