Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells

Abstract

Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb, whereas neocortical adult neurogenesis remains controversial. Several occurrences of neocortical adult neurogenesis in injured neocortex were recently reported, suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that can be activated by injury are maintained in the adult brain. However, it is not clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in the neocortical layer 1 of adult rats and observed that their proliferation was highly activated by global forebrain ischemia. Using retrovirus-mediated labeling of layer 1 proliferating cells with membrane-targeted green fluorescent protein, we found that the newly generated neurons were GABAergic and that the neurons were functionally integrated into the neuronal circuitry. Our results suggest that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions.

The age and genomic integrity of neurons after cortical stroke in humans

“…The present data uncover that, contrary to some experimental studies in animal models 14,15 , the adult human neocortex is incapable of regenerating neurons, even in response to stroke. Moreover, although we found evidence for DNA fragmentation and repair in neurons in the penumbra of the stroke, their genomic DNA had a 14 C concentration corresponding to the time of birth of the individual.…”

Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain

“…Spontaneous (constitutive) parenchymal neurogenesis can be considered a rare phenomenon in mammals, with its regional location being dependent on the animal species (reviewed in Bonfanti and Peretto 2011;Bonfanti 2013;and summarized in Table 1). Different examples of neurogenesis occurring outside of the two germinal-layer-derived neurogenic sites have been described in rodents (Dayer et al 2005;Kokoeva et al 2005), rabbits (Luzzati et al 2006;Ponti et al 2008), and monkeys (Gould et al 2001;Bernier et al 2002), with remarkable differences between closely related orders (e.g., rodents and lagomorphs: cf., for example, Dayer et al 2005;Luzzati et al 2006;Ohira et al 2010;Ponti et al 2008). Some of the differences and discrepancies among studies arise from technical issues, such as analysis of a proliferative marker (e.g., BrdU), colocalization with neuronal markers, or misconception about specific markers (e.g., PSA-NCAM labeling migrating cells and not newborn neurons).…”

“…In adult rodents, most parenchymal neurogenesis seems to occur spontaneously at very low levels, rather being elicited/enhanced after specific physiological or pathological conditions (see below) (Dayer et al 2005;Kokoeva et al 2005;Luzzati et al 2006;Ponti et al 2008;Ohira et al 2010;Pierce and Xu 2010). Dayer and colleagues (2005) showed the occurrence of new neurons in the deep layers of the rat cerebral cortex.…”

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

“…However, an intriguing study identified neural progenitor cells in the neocortical layer 1 of adult rats subjected to mild ischemia. 48 These cells were shown to migrate radially into cortical layers 2-6 and differentiate into a subtype of GABAergic interneurons. The authors showed that proliferating cells in layer 1 are not derived from SVZ NSCs or progenitors, but rather from local progenitors that do not differentiate under normal conditions.…”