scholarly journals Continual reelin signaling by the prime neurogenic niche of the adult brain

2021 ◽  
Author(s):  
F. Javier Perez-Martinez ◽  
Manuel Cifuentes ◽  
Juan M. Luque
Keyword(s):  
Neural Progenitor Cells ◽  
Adult Brain ◽  
Neurogenic Niche ◽  
Lateral Ventricles ◽  
Subependymal Zone ◽  
Reelin Signaling ◽  
Ependymal Cilia ◽  
Newborn Neurons ◽  
Intraventricular Infusion ◽  
Migratory Stream

During development reelin sets the pace of neocortical neurogenesis enabling in turn newborn neurons to migrate, but whether and, if so, how reelin signaling affects the adult neurogenic niches remains uncertain. We show that reelin signaling, resulting in Dab1 phosphorylation, occurs in the ependymal-subependymal zone (EZ/SEZ) of the lateral ventricles where, along with its associated rostral migratory stream (RMS), the highest density of functional ApoER2 accumulates. Mice deficient for reelin, ApoER2 or Dab1 exhibit enlarged ventricles and dysplastic RMS. Moreover, while the conditional ablation of Dab1 in neural progenitor cells (NPCs) enlarges the ventricles and impairs neuroblasts clearance from the SEZ, the transgenic misexpression of reelin in NPCs of reelin-deficient mice normalizes the ventricular lumen and the density of ependymal cilia, ameliorating in turn neuroblasts migration; consistently, intraventricular infusion of reelin reroutes neuroblasts. These results demonstrate that reelin signaling persists sustaining the germinal niche of the lateral ventricles and influencing neuroblasts migration in the adult brain.

scholarly journals A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells

2019 ◽  
Vol 5 (2) ◽  
pp. eaav4416 ◽  
Author(s):  
Jian Dong ◽  
Yuan-Bo Pan ◽  
Xin-Rong Wu ◽  
Li-Na He ◽  
Xian-Dong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Granule Cells ◽  
Adult Brain ◽  
Cell Contact ◽  
External Signal ◽  
Neurogenic Niche ◽  
Functional Transition ◽  
Newborn Neurons ◽  
Cell Cell

The quiescence of radial neural stem cells (rNSCs) in adult brain is regulated by environmental stimuli. However, little is known about how the neurogenic niche couples the external signal to regulate activation and transition of quiescent rNSCs. Here, we reveal that long-term excitation of hippocampal dentate granule cells (GCs) upon voluntary running leads to activation of adult rNSCs in the subgranular zone and thereby generation of newborn neurons. Unexpectedly, the role of these excited GC neurons in NSCs depends on direct GC-rNSC interaction in the local niche, which is through down-regulated ephrin-B3, a GC membrane–bound ligand, and attenuated transcellular EphB2 kinase–dependent signaling in the adjacent rNSCs. Furthermore, constitutively active EphB2 kinase sustains the quiescence of rNSCs during running. These findings thus elucidate the physiological significance of GC excitability on adult rNSCs under external environments and indicate a key-lock switch regulation via cell-cell contact for functional transition of rNSCs.

scholarly journals A role for Lin28a in aging-associated decline of adult hippocampal neurogenesis

2022 ◽  
Author(s):  
Zhechun Hu ◽  
Jiao Ma ◽  
Huimin Yue ◽  
Xiaofang Li ◽  
Chao Wang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Rna Binding ◽  
Functional Integration ◽  
Neural Progenitor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Neurogenic Niche ◽  
Newborn Neurons

Hippocampal neurogenesis declines with aging. Wnt ligands and antagonists within the hippocampal neurogenic niche regulate the proliferation of neural progenitor cells and the development of new neurons, and the changes of their levels in the niche mediate aging-associated decline of neurogenesis. We found that RNA-binding protein Lin28a remained existent in neural progenitor cells and granule neurons in the adult hippocampus, and decreased with aging. Loss of Lin28a inhibited the responsiveness of neural progenitor cells to niche Wnt agonist and reduced neurogenesis, thus impairing pattern separation. Overexpression of Lin28a increased the proliferation of neural progenitor cells, promoted the functional integration of newborn neurons, restored neurogenesis in Wnt-deficient dentate gyrus, and rescued the impaired pattern separation in aging mice. Our data suggest that Lin28a regulates adult hippocampal neurogenesis as an intracellular mechanism by responding to niche Wnt signals, and its decrease is involved in aging-associated decline of hippocampal neurogenesis as well as related cognitive functions.

Is adult hippocampal neurogenesis really relevant for the treatment of psychiatric disorders?

2020 ◽  
Vol 18 ◽  
Author(s):  
Marco Carli ◽  
Stefano Aringhieri ◽  
Shivakumar Kolachalam ◽  
Biancamaria Longoni ◽  
Giovanna Grenno ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Emotional Processing ◽  
Imaging Techniques ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Mood Stabilizers ◽  
Post Traumatic Stress ◽  
Newborn Neurons ◽  
Hippocampal Circuitry

: Adult neurogenesis consists in the generation of newborn neurons from neural stem cells taking place in the adult brain. In mammals, this process is limited to very few areas of the brain, and one of these neurogenic niches is the subgranular layer of the dentate gyrus (DG) of the hippocampus. Adult newborn neurons are generated from quiescent neural progenitors (QNPs), which differentiate through different steps into mature granule cells (GCs), to be finally integrated into the existing hippocampal circuitry. In animal models, adult hippocampal neurogenesis (AHN) is relevant for pattern discrimination, cognitive flexibility, emotional processing and resilience to stressful situations. Imaging techniques allow to visualize newborn neurons within the hippocampus through all their stages of development and differentiation. In humans, the evidence of AHN is more challenging, and, based on recent findings, it persists through the adulthood, even if it declines with age. Whether this process has an important role in human brain function and how it integrates into the existing hippocampal circuitry is still a matter of exciting debate. Importantly, AHN deficiency has been proposed to be relevant in many psychiatric disorders, including mood disorders, anxiety, post-traumatic stress disorder and schizophrenia. This review aims to investigate how AHN is altered in different psychiatric conditions and how pharmacological treatments can rescue this process. In fact, many psychoactive drugs, such as antidepressants, mood stabilizers and atypical antipsychotics (AAPs), can boost AHN with different results. In addition, some non-pharmacological approaches are discussed as well.

scholarly journals Relationships between dietary macronutrients and adult neurogenesis in the regulation of energy metabolism – CORRIGENDUM

2013 ◽  
Vol 111 (4) ◽  
pp. 755-755
Author(s):  
Marianne A. Yon ◽  
Suzanna L. Mauger ◽  
Lucy C. Pickavance
Keyword(s):  
Body Weight ◽  
Energy Metabolism ◽  
Adult Neurogenesis ◽  
Brain Regions ◽  
The Body ◽  
Adult Brain ◽  
Metabolic Dysfunction ◽  
Neurogenic Niche ◽  
Normal Limits ◽  
Simple Carbohydrates

Of the environmental factors which have an impact on body weight, nutrients are most influential. Within normal limits, hypothalamic and related neuronal populations correct perturbations in energy metabolism, to return the body to its nutritional set-point, either through direct response to nutrients or indirectly via peripheral appetite signals. Excessive intake of certain macronutrients, such as simple carbohydrates and SFA, can lead to obesity and attendant metabolic dysfunction, also reflected in alterations in structural plasticity, and, intriguingly, neurogenesis, in some of these brain regions. Neurogenesis, previously thought to occur only in the embryo, is now known to take place in the adult brain, dependent on numerous stimulating and inhibiting factors, including dietary components. Because of classic associations between neurogenesis and the hippocampus, in learning and cognition, this brain region has also been the focus of attention in the study of links between diet and neurogenesis. Recently, however, a more complete picture of this relationship has been building: not only has the hypothalamus been shown to satisfy the criteria for a neurogenic niche, but appetite-related mediators, including circulating hormones, such as leptin and ghrelin, pro-inflammatory cytokines and the endocannabinoid intracellular messengers, are also being examined for their potential role in mediating neurogenic responses to macronutrients. The present review draws together these observations and investigates whether n-3 PUFA may exert their attenuating effects on body weight through the stimulation of adult neurogenesis. Exploration of the effects of nutraceuticals on neurogenic brain regions may encourage the development of new rational therapies in the fight against obesity.

Maternal exposure to methylmercury causes an impairment in ependymal cilia motility in the third ventricle and dilation of lateral ventricles in mice offspring

2020 ◽  
Vol 112 (16) ◽  
pp. 1253-1259
Author(s):  
Teruki Hagiwara ◽  
Hajime Hagino ◽  
Kaho Ueda ◽  
Mina Nakama ◽  
Takeshi Minami
Keyword(s):  
Third Ventricle ◽  
Maternal Exposure ◽  
The Third ◽  
Lateral Ventricles ◽  
Ependymal Cilia

scholarly journals Methylmercury Impact on Adult Neurogenesis: Is the Worst Yet to Come From Recent Brazilian Environmental Disasters?

2020 ◽  
Vol 12 ◽  
Author(s):  
Ramon da Silva Raposo ◽  
Daniel Vieira Pinto ◽  
Ricardo Moreira ◽  
Ronaldo Pereira Dias ◽  
Carlos Alberto Fontes Ribeiro ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Human Health ◽  
Large Scale ◽  
Brain Aging ◽  
Adult Brain ◽  
Neurogenic Niche ◽  
Environmental Disasters ◽  
Neurodevelopmental Abnormalities ◽  
To Come ◽  
The Impact

Worldwide environmental tragedies of anthropogenic origin causing massive release of metals and other pollutants have been increasing considerably. These pollution outbreaks affect the ecosystems and impact human health. Among those tragedies, recent large-scale environmental disasters in Brazil strongly affected riverside populations, leading to high-risk exposure to methylmercury (MeHg). MeHg is highly neurotoxic to the developing brain. This toxicant causes neural stem cell dysfunction and neurodevelopmental abnormalities. However, less is known about the effects of MeHg in the postnatal neurogenic niche, which harbors neural stem cells and their progeny, in the adult brain. Therefore, taking in consideration the impact of MeHg in human health it is urgent to clarify possible associations between exposure to mercury, accelerated cognitive decline, and neurodegenerative diseases. In this perspectives paper, we discuss the neurotoxic mechanisms of MeHg on postnatal neurogenesis and the putative implications associated with accelerated brain aging and early-onset cognitive decline in populations highly exposed to this environmental neurotoxicant.

scholarly journals Engraftment of enteric neural progenitor cells into the injured adult brain

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Jaime Belkind-Gerson ◽  
Ryo Hotta ◽  
Michael Whalen ◽  
Naema Nayyar ◽  
Nandor Nagy ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Adult Brain

scholarly journals Astrocytes at the Hub of the Stress Response: Potential Modulation of Neurogenesis by miRNAs in Astrocyte-Derived Exosomes

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Alejandro Luarte ◽  
Pablo Cisternas ◽  
Ariel Caviedes ◽  
Luis Federico Batiz ◽  
Carlos Lafourcade ◽  
...  
Keyword(s):  
Neural Progenitor Cells ◽  
Nodal Point ◽  
Unipolar Depression ◽  
Neurogenic Niche ◽  
Brain Functions ◽  
Direct Cell ◽  
Repetitive Stress ◽  
Stress Signals ◽  
Systemic Stress ◽  
The Impact

Repetitive stress negatively affects several brain functions and neuronal networks. Moreover, adult neurogenesis is consistently impaired in chronic stress models and in associated human diseases such as unipolar depression and bipolar disorder, while it is restored by effective antidepressant treatments. The adult neurogenic niche contains neural progenitor cells in addition to amplifying progenitors, neuroblasts, immature and mature neurons, pericytes, astrocytes, and microglial cells. Because of their particular and crucial position, with their end feet enwrapping endothelial cells and their close communication with the cells of the niche, astrocytes might constitute a nodal point to bridge or transduce systemic stress signals from peripheral blood, such as glucocorticoids, to the cells involved in the neurogenic process. It has been proposed that communication between astrocytes and niche cells depends on direct cell-cell contacts and soluble mediators. In addition, new evidence suggests that this communication might be mediated by extracellular vesicles such as exosomes, and in particular, by their miRNA cargo. Here, we address some of the latest findings regarding the impact of stress in the biology of the neurogenic niche, and postulate how astrocytic exosomes (and miRNAs) may play a fundamental role in such phenomenon.

Sign in / Sign up

Export Citation Format

Share Document