scholarly journals Phosphodiesterase7 Inhibition Activates Adult Neurogenesis in Hippocampus and Subventricular Zone In Vitro and In Vivo

Stem Cells ◽  
2016 ◽  
Vol 35 (2) ◽  
pp. 458-472 ◽  
Author(s):  
Jose A. Morales-Garcia ◽  
Victor Echeverry-Alzate ◽  
Sandra Alonso-Gil ◽  
Marina Sanz-SanCristobal ◽  
Jose A. Lopez-Moreno ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone

Cortical and Subventricular Zone Glioblastoma-Derived Stem-Like Cells Display Different Molecular Profiles and Differential In Vitro and In Vivo Properties

2011 ◽  
Vol 19 (S3) ◽  
pp. 608-619 ◽  
Author(s):  
Aurélie Tchoghandjian ◽  
Nathalie Baeza-Kallee ◽  
Christophe Beclin ◽  
Philippe Metellus ◽  
Carole Colin ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Molecular Profiles

scholarly journals AAV ablates neurogenesis in the adult murine hippocampus

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Stephen Johnston ◽  
Sarah Parylak ◽  
Stacy Kim ◽  
Nolan Mac ◽  
Christina Lim ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cell Death ◽  
Adult Neurogenesis ◽  
Granule Cells ◽  
Viral Vector ◽  
Cell Types ◽  
Early Gene ◽  
Post Injection

Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hours post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentate gyrus (DG)-without ablating adult neurogenesis-can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo 2-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system (CNS) should be carefully evaluated.

scholarly journals Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Fabio Cavaliere ◽  
Monica Benito-Muñoz ◽  
Carlos Matute
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Neural Regeneration ◽  
Cell Populations ◽  
Subgranular Zone ◽  
Organotypic Cultures ◽  
Cellular Mechanisms ◽  
Cns Disorders ◽  
Pathological Conditions

Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn toin vitromodels. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

scholarly journals N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jose A. Morales-Garcia ◽  
Javier Calleja-Conde ◽  
Jose A. Lopez-Moreno ◽  
Sandra Alonso-Gil ◽  
Marina Sanz-SanCristobal ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Spatial Learning And Memory ◽  
South American ◽  
New Production ◽  
Sigma 1 Receptor ◽  
Neurogenic Niche ◽  
Sigma 1 ◽  
Functional Relevance

Abstract N,N-dimethyltryptamine (DMT) is a component of the ayahuasca brew traditionally used for ritual and therapeutic purposes across several South American countries. Here, we have examined, in vitro and vivo, the potential neurogenic effect of DMT. Our results demonstrate that DMT administration activates the main adult neurogenic niche, the subgranular zone of the dentate gyrus of the hippocampus, promoting newly generated neurons in the granular zone. Moreover, these mice performed better, compared to control non-treated animals, in memory tests, which suggest a functional relevance for the DMT-induced new production of neurons in the hippocampus. Interestingly, the neurogenic effect of DMT appears to involve signaling via sigma-1 receptor (S1R) activation since S1R antagonist blocked the neurogenic effect. Taken together, our results demonstrate that DMT treatment activates the subgranular neurogenic niche regulating the proliferation of neural stem cells, the migration of neuroblasts, and promoting the generation of new neurons in the hippocampus, therefore enhancing adult neurogenesis and improving spatial learning and memory tasks.

scholarly journals Mimicking Neural Stem Cell Niche by Biocompatible Substrates

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Citlalli Regalado-Santiago ◽  
Enrique Juárez-Aguilar ◽  
Juan David Olivares-Hernández ◽  
Elisa Tamariz
Keyword(s):  
Subventricular Zone ◽  
Current Knowledge ◽  
Ventricular Zone ◽  
Neurogenic Niche ◽  
Extracellular Matrix Components ◽  
The Central Nervous System ◽  
Cell Niche ◽  
Extracellular Environment

Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to buildingin vitromodels that include the relevant components of thein vivoniche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for thein vitroandin vivomimicking of extracellular NSCs conditions.

scholarly journals Activated Neural Stem Cells Contribute to Stroke-Induced Neurogenesis and Neuroblast Migration toward the Infarct Boundary in Adult Rats

2004 ◽  
Vol 24 (4) ◽  
pp. 441-448 ◽  
Author(s):  
Ruilan Zhang ◽  
Zhenggang Zhang ◽  
Lei Wang ◽  
Ying Wang ◽  
Anton Gousev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Subventricular Zone ◽  
Proliferating Cells ◽  
Adult Rats ◽  
Antimitotic Agent ◽  
Neuroblast Migration ◽  
Ipsilateral Striatum

Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum. Infusion of an antimitotic agent (cytosine-β-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum. However, doublecortin-positive cells rapidly replenished after antimitotic agent depletion of actively proliferating cells. Depleting the numbers of actively proliferating cells in vivo had no effect on the numbers of neurospheres formed in vitro, yet the numbers of neurospheres derived from stroke rats significantly ( P < 0.05) increased. Neurospheres derived from stroke rats self-renewed and differentiated into neurons and glia. In addition, doublecortin-positive cells generated in the SVZ migrated in a chainlike structure toward ischemic striatum. These findings indicate that in the adult stroke brain, increases in recruitment of neural stem cells contribute to stroke-induced neurogenesis, and that newly generated neurons migrate from the SVZ to the ischemic striatum.

scholarly journals A new function for Prokineticin 2: recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury

2018 ◽  
Author(s):  
Mayara Vieira Mundim ◽  
Laura Nicoleti Zamproni ◽  
Agnes Araújo Sardinha Pinto ◽  
Layla Testa Galindo ◽  
André Machado Xavier ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Subventricular Zone ◽  
Brain Injuries ◽  
Rostral Migratory Stream ◽  
Subgranular Zone ◽  
Prokineticin 2 ◽  
Migratory Stream

AbstractTraumatic brain injury is an important cause of mortality and morbidity all over the world. After the initial injury there is a cascade of cellular and molecular events that ultimately lead to cell death. Therapies aim not only to counteract these mechanisms but also to replenish the lost cell population in order to achieve a better recovery. The adult mammal brain in not as plastic as the postnatal, but it has at least two neurogenic regions that maintains physiological functions in the brain; the subgranular zone of the dentate gyrus of the hippocampus, which produces neurons that integrate locally, and the subventricular zone (SVZ) of the lateral ventricles, that produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulbs. Brain injuries, as well as neurodegenerative diseases, induce the SVZ to respond by increasing cell proliferation and migration to the injured areas. Here we report that SVZ cells migrate to the injured cortex after traumatic brain injury in mice, and that the physiological RMS migration is not impaired. We also show that Prokineticin 2 (PROK2), a chemokine important for the olfactory bulb neurogenesis by promoting the directional migration of neuroblasts, is induced in the injured cortex. Using PROK2 receptor antagonist and recombinant PROK2 we show for the first time that PROK2 can directionally attract SVZ cells in vitro and in vivo. The data we present here links one more element of the inflammatory process, PROK2 secreted by microglia, to the attempt to regenerate an acutely injured mammalian cortex.AbbreviationsSGZsubgranular zoneSVZsubventricular zoneRMSrostral migratory streamPROK2Prokineticin 2

Dysfunction of the proteoglycan Tsukushi causes hydrocephalus through altered neurogenesis in the subventricular zone in mice

2021 ◽  
Vol 13 (587) ◽  
pp. eaay7896
Author(s):  
Naofumi Ito ◽  
M. Asrafuzzaman Riyadh ◽  
Shah Adil Ishtiyaq Ahmad ◽  
Satoko Hattori ◽  
Yonehiro Kanemura ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Stem Cell ◽  
Growth Factors ◽  
Subventricular Zone ◽  
Physiological Activity ◽  
Neurodevelopmental Disorder ◽  
Ependymal Cells ◽  
Wild Type

The lateral ventricle (LV) is flanked by the subventricular zone (SVZ), a neural stem cell (NSC) niche rich in extrinsic growth factors regulating NSC maintenance, proliferation, and neuronal differentiation. Dysregulation of the SVZ niche causes LV expansion, a condition known as hydrocephalus; however, the underlying pathological mechanisms are unclear. We show that deficiency of the proteoglycan Tsukushi (TSK) in ependymal cells at the LV surface and in the cerebrospinal fluid results in hydrocephalus with neurodevelopmental disorder-like symptoms in mice. These symptoms are accompanied by altered differentiation and survival of the NSC lineage, disrupted ependymal structure, and dysregulated Wnt signaling. Multiple TSK variants found in patients with hydrocephalus exhibit reduced physiological activity in mice in vivo and in vitro. Administration of wild-type TSK protein or Wnt antagonists, but not of hydrocephalus-related TSK variants, in the LV of TSK knockout mice prevented hydrocephalus and preserved SVZ neurogenesis. These observations suggest that TSK plays a crucial role as a niche molecule modulating the fate of SVZ NSCs and point to TSK as a candidate for the diagnosis and therapy of hydrocephalus.

scholarly journals Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers

2019 ◽  
Vol 27 (3) ◽  
pp. 934-948 ◽  
Author(s):  
Chiara Scopa ◽  
Francesco Marrocco ◽  
Valentina Latina ◽  
Federica Ruggeri ◽  
Valerio Corvaglia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Point Of View ◽  
Early Event ◽  
Aβ Oligomers ◽  
Promising Therapeutic Target ◽  
Presymptomatic Stage

Abstract Alterations of adult neurogenesis have been reported in several Alzheimer's disease (AD) animal models and human brains, while defects in this process at presymptomatic/early stages of AD have not been explored yet. To address this, we investigated potential neurogenesis defects in Tg2576 transgenic mice at 1.5 months of age, a prodromal asymptomatic age in terms of Aβ accumulation and neurodegeneration. We observe that Tg2576 resident and SVZ-derived adult neural stem cells (aNSCs) proliferate significantly less. Further, they fail to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. Olfactory bulb neurogenesis is also strongly reduced, confirming the neurogenic defect in vivo. We find that this phenotype depends on the formation and accumulation of intracellular A-beta oligomers (AβOs) in aNSCs. Indeed, impaired neurogenesis of Tg2576 progenitors is remarkably rescued both in vitro and in vivo by the expression of a conformation-specific anti-AβOs intrabody (scFvA13-KDEL), which selectively interferes with the intracellular generation of AβOs in the endoplasmic reticulum (ER). Altogether, our results demonstrate that SVZ neurogenesis is impaired already at a presymptomatic stage of AD and is caused by endogenously generated intracellular AβOs in the ER of aNSCs. From a translational point of view, impaired SVZ neurogenesis may represent a novel biomarker for AD early diagnosis, in association to other biomarkers. Further, this study validates intracellular Aβ oligomers as a promising therapeutic target and prospects anti-AβOs scFvA13-KDEL intrabody as an effective tool for AD treatment.

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