Ninomiya M, Yamashita T, Araki N, Okano H, Sawamoto KEnhanced neurogenesis in the ischemic striatum following EGF-induced expansion of transit-amplifying cells in the subventricular zone. Neurosci Lett 403:63-67

Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan.
Neuroscience Letters (Impact Factor: 2.03). 08/2006; 403(1-2):63-7. DOI: 10.1016/j.neulet.2006.04.039
Source: PubMed


In the subventricular zone (SVZ) of the adult mammalian brain, neural stem cells continually produce transit-amplifying precursors, which generate neuroblasts migrating into the olfactory bulb. Previous studies have suggested that SVZ cells also have the capacity to generate some striatal neurons after cerebral ischemia. The infusion of epidermal growth factor (EGF) has been demonstrated to increase the number of these regenerated neurons. However, which cell types in the SVZ are stimulated to proliferate or differentiate after EGF infusion remains unknown. In this paper, we demonstrated that cerebral ischemia results in an increase in the number of EGF receptor (EGFR)-positive transit-amplifying cells in the SVZ. EGF infusion into the ischemic brain caused the number of transit-amplifying cells to increase and the number of neuroblasts to decrease. On the other hand, after an interval of 6 days after the discontinuation of EGF infusion, a significant increase in the number of neuroblasts was found, both in the striatum and the SVZ. These results suggest that the replacement of neurons in injured striatum can be enhanced by an EGF-induced expansion of transit-amplifying cells in the SVZ.

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    • "Accumulated evidence suggests that there are multiple neurogenic niches in the brain apart from the hippocampal dentate gyrus sub granular zone (SGZ) and the cerebral sub ventricular zone (SVZ). These include the hypothalamus (Lee et al., 2012), cerebellum (Keller et al., 2004; Ponti et al., 2005, 2006, 2008, 2010; Bonfanti and Ponti, 2008; Hajihosseini et al., 2008), striatum (Tattersfield et al., 2004; Ninomiya et al., 2006; Luzzati et al., 2007; Snyder et al., 2010; Danilov et al., 2012; Delavaran et al., 2013; Ernst et al., 2014; Kempermann, 2014), and SN (Bayer et al., 1995; Zhao et al., 2003; Chen et al., 2005; Van Kampen and Robertson, 2005; Yoshimi et al., 2005; Arias-Carrión et al., 2006, 2009; Freundlieb et al., 2006; Shan et al., 2006; Steiner et al., 2006; Esposito et al., 2007; Mandel et al., 2007; Di Giovanni et al., 2009; Ries et al., 2009; Park et al., 2012; Sun et al., 2012a,b; Worlitzer et al., 2013). Therefore, APα may promote the generation of new cells locally in SN. "
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    ABSTRACT: Reinstalling the neurobiological circuits to effectively change the debilitating course of neurodegenerative diseases is of utmost importance. This reinstallation requires generation of new cells which are able to differentiate into specific types of neurons and modification of the local environment suitable for integration of these new neurons into the neuronal circuits. Allopregnanolone (APα) seems to be involved in both of these processes, and therefore, is a potential neurotrophic agent. Loss of dopamine neurons in the substantia nigra (SN) is one of the main pathological features of Parkinson's and also in, at least, a subset of Alzheimer's patients. Therefore, reinstallation of the dopamine neurons in nigrostriatal tract is of unique importance for these neurodegenerative diseases. However, for the neurogenic status and the roles of allopregnanolone in the nigrostriatal tract, the evidence is accumulating and debating. This review summarizes recent studies regarding the neurogenic status in the nigrostriatal tract. Furthermore, special attention is placed on evidence suggesting that reductions in allopregnenalone levels are one of the major pathological features in PD and AD. This evidence has also been confirmed in brains of mice that were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or those bearing neurodegenerative mutations. Lastly, we highlight studies showing that allopregnanalone can augment the number of total cells and dopaminergic neurons via peripheral exogenous administration.
    Frontiers in Cellular Neuroscience 08/2014; 8:224. DOI:10.3389/fncel.2014.00224 · 4.29 Impact Factor
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    • "These cells may be a sub-population of SVZ NSPCs, the NG2+ oligodendrocyte progenitors, which express EGFR and are induced to migrate in response to EGF (Aguirre et al., 2005, 2007). Conversely, in the damaged brain, such as following ischemia, EGF promoted SVZ NPC proliferation with subsequent production of neuroblasts in SVZ and striatum (Ninomiya et al., 2006), also it induced migration of doublecortin positive precursors and their subsequent long term (13 weeks) survival as parvalbumin-expressing interneurons (Teramoto et al., 2003). A similar infusion following traumatic brain injury also induced SVZ proliferation, as well as SGZ proliferation, at early timepoints but did not promote longer term (4 weeks survival) of the newborn SGZ cells, many of which had differentiated into astrocytes rather than neurons (Sun et al., 2010). "
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    ABSTRACT: Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation.
    Frontiers in Cellular Neuroscience 12/2012; 6:70. DOI:10.3389/fncel.2012.00070 · 4.29 Impact Factor
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    • "Brains were perfusion-fixed with 4% paraformaldehyde, postfixed in the same fixative overnight, and 50 µm sections were cut on a Vibratome sectioning system (VT1200S; Leica, Heidelberg, Germany) as described previously [17] [38] [39]. After three rinses in PBS, the sections were incubated for 40 min in blocking solution (PBS containing 10% donkey serum and 0.2% Triton X-100) and then overnight at 4 • C with primary antibodies, which were diluted in the same solution. "
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    ABSTRACT: Recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain. Some of these new neurons migrate to injured brain tissues and differentiate into mature neurons, suggesting that such new neurons may be able to replace neurons lost to degenerative disease or injury and improve or repair neurological deficits. Here, we tested whether delivering growth factors via gelatin hydrogel microspheres would support neurogenesis in the SVZ. Insulin-like growth factor-1 (IGF-1)-containing microspheres increased the number of new neurons in the SVZ. Hepatocyte growth factor (HGF)-containing microspheres increased the number of new neurons migrating from the SVZ towards the injured striatum in a stroke model in mouse. These results suggest that the strategy of using gelatin hydrogel microspheres to achieve the sustained release of growth factors holds promise for the clinical regeneration of damaged brain tissues from endogenous neural stem cells in the adult SVZ.
    10/2012; 2012(6):915160. DOI:10.1155/2012/915160
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