Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction

Delgado, Ana C.; Ferrón, Sacri R.; Vicente, Diana; Porlan, Eva; Pérez-Villalba, Ana; Trujillo, Carmen María; D’Ocón, Pilar; Fariñas, Isabel

doi:10.1016/j.neuron.2014.06.015

Cited by 164 publications

(143 citation statements)

References 53 publications

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“…Recent work in mice has begun to identify choroid plexus-derived factors that regulate adult neural stem cell proliferation and differentiation. Choroid plexus-derived interleukin 1β and neurotrophin 3 in the CSF promote neural stem cell quiescence [35,69]. Importantly, the LVCP is emerging as a key niche compartment of the adult V-SVZ, which not only affects stem cells, but also each stage of the lineage [137].…”

Section: Adultmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

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Section: Adultmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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“…1073/pnas.1609592113/-/DCSupplemental. (11,17) and ephrinB2/Jagged1 (16) or NT-3 signaling (18). Less is known, however, regarding the nature of physical NSC-BV engagements and communication modes in the DG niche.…”

mentioning

confidence: 99%

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

Licht

Rothe

Kreisel

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal "juvenile" NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an "aged" systemic milieu.adult neurogenesis | VEGF | neurovascular | aging | neural stem cells T he reserve of neuronal stem cells (NSCs) in the hippocampal dentate gyrus (DG) continues to produce neuroblasts maturing into functional neurons after birth. Adult hippocampal neurogenesis, however, rapidly declines with age, and in the rodent brain, it is barely detected beyond 8 mo of age (1-4). Several factors, including BDNF, FGF, insulin-like growth factor, VEGF, and others, were shown to enhance the basal level of hippocampal neurogenesis (reviewed in ref. 5). However, there is no report of a factor capable of inducing sustained neurogenic enhancement lasting months after its withdrawal.It has been shown that age-related decrease in hippocampal neurogenesis is associated with progressive depletion of the finite NSC pool due to the fact that neuroblast-producing asymmetrical NSC divisions can only take place a limited number of times before their terminal differentiation to astrocytes (2). Supporting the notion of an exhaustible NSC reservoir is also a study showing that experimentally forced accelerated neurogenesis results in premature NSC depletion (6) and a study showing that experimentally induced epilepsy is associated with premature NSC exhaustion (7). Balancing this deterministic view, however, certain genetic manipulations [e.g., experimental phosphatase and tensin homolog (PTEN) deletion] were shown to increase NSC number by symmetrical divisions (8). It thus remains unclear whether there are means to enforce enhanced hippocampal neurogenesis for a long period without necessarily causing premature exhaustion of the NSC reservoir and a resultant accelerated age-related neurogenic decay.

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“…However, whether the angiocrine signals in the adult and embryonic niches are similar or distinct remains to be established. In particular, it will be interesting to examine whether embryonic NPCs respond to contact-dependent vascular regulation via notch-delta signalling [91] or endothelial cytokines such as PEDF, PLGF, BDNF or NTF3 [94][95][96][97], which are all key for stem and progenitor cell regulation in the adult neurogenic niche. This is an important consideration, because findings made in the adult brain are not necessarily predictive of angiocrine regulation of NPCs in utero, as demonstrated, for example, by the divergent roles of NTF3 during adult and embryonic neurogenesis [97,98].…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between blood vessels and neural progenitors in the developing brain

Tata¹,

Ruhrberg²

2018

Neuronal Signaling

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The formation of the central nervous system (CNS) involves multiple cellular and molecular interactions between neural progenitor cells (NPCs) and blood vessels to establish extensive and complex neural networks and attract a vascular supply that support their function. In this review, we discuss studies that have performed genetic manipulations of chick, fish and mouse embryos to define the spatiotemporal roles of molecules that mediate the reciprocal regulation of NPCs and blood vessels. These experiments have highlighted core functions of NPC-expressed ligands in initiating vascular growth into and within the neural tube as well as establishing the blood-brain barrier. More recent findings have also revealed indispensable roles of blood vessels in regulating NPC expansion and eventual differentiation, and specific regional differences in the effect of angiocrine signals. Accordingly, NPCs initially stimulate blood vessel growth and maturation to nourish the brain, but blood vessels subsequently also regulate NPC behaviour to promote the formation of a sufficient number and diversity of neural cells. A greater understanding of the molecular cross-talk between NPCs and blood vessels will improve our knowledge of how the vertebrate nervous system forms and likely help in the design of novel therapies aimed at regenerating neurons and neural vasculature following CNS disease or injury.

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Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction

Cited by 164 publications

References 53 publications

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

Cross-talk between blood vessels and neural progenitors in the developing brain

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