Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain

Abstract Understanding the migration of newborn neurons within the brain presents a major challenge in contemporary biology. Neuronal migration is widespread within the developing brain but is also important within the adult brain. For instance, stem cells within the ventricular–subventricular zone (V-SVZ) and the subgranular zone of dentate gyrus of the adult rodent brain produce neuroblasts that migrate to the olfactory bulb and granule cell layer of the dentate gyrus, respectively, where they regulate key brain functions including innate olfactory responses, learning, and memory. Critically, our understanding of the factors mediating neuroblast migration remains limited. The transcription factor nuclear factor I X (NFIX) has previously been implicated in embryonic cortical development. Here, we employed conditional ablation of Nfix from the adult mouse brain and demonstrated that the removal of this gene from either neural stem and progenitor cells, or neuroblasts, within the V-SVZ culminated in neuroblast migration defects. Mechanistically, we identified aberrant neuroblast branching, due in part to increased expression of the guanylyl cyclase natriuretic peptide receptor 2 (Npr2), as a factor contributing to abnormal migration in Nfix-deficient adult mice. Collectively, these data provide new insights into how neuroblast migration is regulated at a transcriptional level within the adult brain.

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Meteorin is a Chemokinetic Factor in Neuroblast Migration and Promotes Stroke-Induced Striatal Neurogenesis

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2011.156 ◽

2011 ◽

Vol 32 (2) ◽

pp. 387-398 ◽

Cited By ~ 28

Author(s):

Zhaolu Wang ◽

Nuno Andrade ◽

Malene Torp ◽

Somsak Wattananit ◽

Andreas Arvidsson ◽

...

Keyword(s):

Neural Progenitor Cells ◽

Apoptotic Cell ◽

Artery Occlusion ◽

Adult Brain ◽

Adult Rats ◽

Neuroblast Migration ◽

Mature Neurons ◽

Cerebral Artery Occlusion

Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-d-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.

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Intrinsic Mechanisms Regulating Neuronal Migration in the Postnatal Brain

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2020.620379 ◽

2021 ◽

Vol 14 ◽

Author(s):

Cedric Bressan ◽

Armen Saghatelyan

Keyword(s):

Neuronal Migration ◽

Adult Brain ◽

Long Distance ◽

Postnatal Brain ◽

Early Postnatal Development ◽

Neuroblast Migration ◽

Mitochondria Dynamics ◽

Cytoskeleton Remodeling ◽

A Site ◽

Migratory Stream

Neuronal migration is a fundamental brain development process that allows cells to move from their birthplaces to their sites of integration. Although neuronal migration largely ceases during embryonic and early postnatal development, neuroblasts continue to be produced and to migrate to a few regions of the adult brain such as the dentate gyrus and the subventricular zone (SVZ). In the SVZ, a large number of neuroblasts migrate into the olfactory bulb (OB) along the rostral migratory stream (RMS). Neuroblasts migrate in chains in a tightly organized micro-environment composed of astrocytes that ensheath the chains of neuroblasts and regulate their migration; the blood vessels that are used by neuroblasts as a physical scaffold and a source of molecular factors; and axons that modulate neuronal migration. In addition to diverse sets of extrinsic micro-environmental cues, long-distance neuronal migration involves a number of intrinsic mechanisms, including membrane and cytoskeleton remodeling, Ca2+ signaling, mitochondria dynamics, energy consumption, and autophagy. All these mechanisms are required to cope with the different micro-environment signals and maintain cellular homeostasis in order to sustain the proper dynamics of migrating neuroblasts and their faithful arrival in the target regions. Neuroblasts in the postnatal brain not only migrate into the OB but may also deviate from their normal path to migrate to a site of injury induced by a stroke or by certain neurodegenerative disorders. In this review, we will focus on the intrinsic mechanisms that regulate long-distance neuroblast migration in the adult brain and on how these pathways may be modulated to control the recruitment of neuroblasts to damaged/diseased brain areas.

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Lentiviral Transduction of Neurons in Adult Brain: Evaluation of Inflammatory Response and Cognitive Effects in Mice

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-016-3404-4 ◽

2016 ◽

Vol 161 (2) ◽

pp. 316-319 ◽

Cited By ~ 3

Author(s):

T. A. Kunitsyna ◽

O. I. Ivashkina ◽

M. A. Roshchina ◽

K. A. Toropova ◽

K. V. Anokhin

Keyword(s):

Inflammatory Response ◽

Adult Brain ◽

Cognitive Effects ◽

Lentiviral Transduction

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Relationship between Blood Vessels and Migration of Neuroblasts in the Olfactory Neurogenic Region of the Rodent Brain

International Journal of Molecular Sciences ◽

10.3390/ijms222111506 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11506

Author(s):

Marcela Martončíková ◽

Anna Alexovič Matiašová ◽

Juraj Ševc ◽

Enikő Račeková

Keyword(s):

Blood Vessels ◽

Radial Glia ◽

Postnatal Period ◽

Adult Brain ◽

Embryonic Period ◽

Neuroblast Migration ◽

Rodent Brain ◽

And Migration ◽

Migratory Stream ◽

Migratory Pathway

Neural precursors originating in the subventricular zone (SVZ), the largest neurogenic region of the adult brain, migrate several millimeters along a restricted migratory pathway, the rostral migratory stream (RMS), toward the olfactory bulb (OB), where they differentiate into interneurons and integrate into the local neuronal circuits. Migration of SVZ-derived neuroblasts in the adult brain differs in many aspects from that in the embryonic period. Unlike in that period, postnatally-generated neuroblasts in the SVZ are able to divide during migration along the RMS, as well as they migrate independently of radial glia. The homophilic mode of migration, i.e., using each other to move, is typical for neuroblast movement in the RMS. In addition, it has recently been demonstrated that specifically-arranged blood vessels navigate SVZ-derived neuroblasts to the OB and provide signals which promote migration. Here we review the development of vasculature in the presumptive neurogenic region of the rodent brain during the embryonic period as well as the development of the vascular scaffold guiding neuroblast migration in the postnatal period, and the significance of blood vessel reorganization during the early postnatal period for proper migration of RMS neuroblasts in adulthood.

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