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

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.

scholarly journals Intrinsic Mechanisms Regulating Neuronal Migration in the Postnatal Brain

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.

scholarly journals Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jui-Chih Chang ◽  
Yi-Chun Chao ◽  
Huei-Shin Chang ◽  
Yu-Ling Wu ◽  
Hui-Ju Chang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Disease Model ◽  
Intranasal Delivery ◽  
The Difference ◽  
And Migration ◽  
6 Hydroxydopamine ◽  
Locomotor Behaviors ◽  
Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

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

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0151589 ◽  
Author(s):  
Kun Zhou ◽  
Sepideh Motamed ◽  
George A. Thouas ◽  
Claude C. Bernard ◽  
Dan Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Adult Brain ◽  
Neuroblast Migration

scholarly journals Cortical Interneuron Development: a role for small Rho GTPases

2021 ◽  
Author(s):  
Zouzana Kounoupa ◽  
Domna Karagogeos
Keyword(s):  
Cell Cycle ◽  
Rho Gtpases ◽  
Double Mutant ◽  
Epileptic Seizures ◽  
Transgenic Animals ◽  
Postnatal Period ◽  
Cell Therapies ◽  
Cortical Interneurons ◽  
Small Rho Gtpases ◽  
And Migration

GABAergic interneurons control cortical excitation/inhibition balance and are implicated in severe neurodevelopmental disorders. In contrast to the multiplicity of signals underlying the generation and migration of cortical interneurons, the intracellular proteins mediating the response to these cues are mostly unknown. We have demonstrated the unique and diverse roles of the Rho GTPases Rac1 and 3 in cell cycle and morphology in transgenic animals where Rac1 and Rac1/3 were ablated specifically in cortical interneurons. In the Rac1 mutant, progenitors delay their cell cycle exit probably due to a prolonged G1 phase resulting in a cortex with 50% reductions in interneurons and an imbalance of excitation/inhibition in cortical circuits. This disruption in GABAergic inhibition alters glutamatergic function in the adult cortex that could be reversed by enhancement of GABAergic function during an early postnatal period. Furthermore, this disruption disturbs the neuronal synchronization in the adult cortex. In the double mutant, additional severe cytoskeletal defects result in an 80% interneuron decrease. Both lines die from epileptic seizures postnatally. We have made progress towards characterizing the cell cycle defect in Rac1 mutant interneuron progenitors, determining the morphological and synaptic characteristics of single and double mutant interneurons and identifying some of the molecular players by which Racs exert their actions by proteomic analysis. In our present work, we review these studies and discuss open questions and future perspectives. We expect that our data will contribute to the understanding of the function of cortical interneurons, especially since preclinical models of interneuron-based cell therapies are being established.

scholarly journals Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells.

1992 ◽  
Vol 118 (4) ◽  
pp. 889-900 ◽  
Author(s):  
G Wolswijk ◽  
M Noble
Keyword(s):  
Progenitor Cells ◽  
Adult Brain ◽  
High Rate ◽  
Adult Rat ◽  
Large Numbers ◽  
Dividing Cells ◽  
Rapid Generation ◽  
And Migration

We have shown previously that oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells isolated from adult rat optic nerves can be distinguished in vitro from their perinatal counterparts on the basis of their much slower rates of division, differentiation, and migration when grown in the presence of cortical astrocytes or PDGF. This behavior is consistent with in vivo observations that there is only a modest production of oligodendrocytes in the adult CNS. As such a behavior is inconsistent with the likely need for a rapid generation of oligodendrocytes following demyelinating damage to the mature CNS, we have been concerned with identifying in vitro conditions that allow O-2Aadult progenitor cells to generate rapidly large numbers of progeny cells. We now provide evidence that many slowly dividing O-2Aadult progenitor cells can be converted to rapidly dividing cells by exposing adult optic nerve cultures to both PDGF and bFGF. In addition, these O-2Aadult progenitor cells appear to acquire other properties of O-2Aperinatal progenitor cells, such as bipolar morphology and high rate of migration. Although many O-2Aadult progenitor cells in cultures exposed to bFGF alone also divide rapidly, these cells are multipolar and migrate little in vitro. Oligodendrocytic differentiation of O-2Aadult progenitor cells, which express receptors for bFGF in vitro, is almost completely inhibited in cultures exposed to bFGF or bFGF plus PDGF. As bFGF and PDGF appear to be upregulated and/or released after injury to the adult brain, this particular in vitro response of O-2Aadult progenitor cells to PDGF and bFGF may be of importance in the generation of large numbers of new oligodendrocytes in vivo following demyelination.

NFIX-Mediated Inhibition of Neuroblast Branching Regulates Migration Within the Adult Mouse Ventricular–Subventricular Zone

2018 ◽  
Vol 29 (8) ◽  
pp. 3590-3604 ◽  
Author(s):  
Oressia Zalucki ◽  
Lachlan Harris ◽  
Tracey J Harvey ◽  
Danyon Harkins ◽  
Jocelyn Widagdo ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Subventricular Zone ◽  
Adult Mouse ◽  
Adult Brain ◽  
Granule Cell Layer ◽  
Transcriptional Level ◽  
Olfactory Responses ◽  
Brain Functions ◽  
Neuroblast Migration ◽  
Adult Mice

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.

scholarly journals The diacylglycerol lipases: structure, regulation and roles in and beyond endocannabinoid signalling

2012 ◽  
Vol 367 (1607) ◽  
pp. 3264-3275 ◽  
Author(s):  
Melina Reisenberg ◽  
Praveen K. Singh ◽  
Gareth Williams ◽  
Patrick Doherty
Keyword(s):  
Dopaminergic Neurons ◽  
Cannabinoid Receptors ◽  
Homology Modelling ◽  
Detailed Examination ◽  
The Body ◽  
Adult Brain ◽  
And Migration ◽  
Regulatory Loop ◽  
Translational Mechanisms ◽  
The Brain

The diacylglycerol lipases (DAGLs) hydrolyse diacylglycerol to generate 2-arachidonoylglycerol (2-AG), the most abundant ligand for the CB 1 and CB 2 cannabinoid receptors in the body. DAGL-dependent endocannabinoid signalling regulates axonal growth and guidance during development, and is required for the generation and migration of new neurons in the adult brain. At developed synapses, 2-AG released from postsynaptic terminals acts back on presynaptic CB 1 receptors to inhibit the secretion of both excitatory and inhibitory neurotransmitters, with this DAGL-dependent synaptic plasticity operating throughout the nervous system. Importantly, the DAGLs have functions that do not involve cannabinoid receptors. For example, 2-AG is the precursor of arachidonic acid in a pathway that maintains the level of this essential lipid in the brain and other organs. This pathway also drives the cyclooxygenase-dependent generation of inflammatory prostaglandins in the brain, which has recently been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. Remarkably, we still know very little about the mechanisms that regulate DAGL activity—however, key insights can be gleaned by homology modelling against other α/β hydrolases and from a detailed examination of published proteomic studies and other databases. These identify a regulatory loop with a highly conserved signature motif, as well as phosphorylation and palmitoylation as post-translational mechanisms likely to regulate function.

scholarly journals Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration

2017 ◽  
Vol 114 (10) ◽  
pp. E2006-E2015 ◽  
Author(s):  
János Hanics ◽  
Edit Szodorai ◽  
Giuseppe Tortoriello ◽  
Katarzyna Malenczyk ◽  
Erik Keimpema ◽  
...  
Keyword(s):  
Annexin V ◽  
Therapeutic Benefit ◽  
Mouse Genetics ◽  
Matrix Metalloprotease ◽  
Loss Of Function ◽  
Neuroblast Migration ◽  
Sensor Protein ◽  
Migratory Stream

The rostral migratory stream (RMS) is viewed as a glia-enriched conduit of forward-migrating neuroblasts in which chemorepulsive signals control the pace of forward migration. Here we demonstrate the existence of a scaffold of neurons that receive synaptic inputs within the rat, mouse, and human fetal RMS equivalents. These neurons express secretagogin, a Ca2+-sensor protein, to execute an annexin V-dependent externalization of matrix metalloprotease-2 (MMP-2) for reconfiguring the extracellular matrix locally. Mouse genetics combined with pharmacological probing in vivo and in vitro demonstrate that MMP-2 externalization occurs on demand and that its loss slows neuroblast migration. Loss of function is particularly remarkable upon injury to the olfactory bulb. Cumulatively, we identify a signaling cascade that provokes structural remodeling of the RMS through recruitment of MMP-2 by a previously unrecognized neuronal constituent. Given the life-long presence of secretagogin-containing neurons in human, this mechanism might be exploited for therapeutic benefit in rescue strategies.

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