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 Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

2020 ◽  
Vol 117 (41) ◽  
pp. 25818-25829
Author(s):  
Xinxing Wang ◽  
Hanxiao Liu ◽  
Johannes Morstein ◽  
Alexander J. E. Novak ◽  
Dirk Trauner ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Energy Homeostasis ◽  
Inhibitory Neuron ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neuron Activity ◽  
Adult Mice ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

scholarly journals Isolation of multipotent neural stem or progenitor cells from both the dentate gyrus and subventricular zone of a single adult mouse

2012 ◽  
Vol 7 (11) ◽  
pp. 2005-2012 ◽  
Author(s):  
Weixiang Guo ◽  
Natalie E Patzlaff ◽  
Emily M Jobe ◽  
Xinyu Zhao
Keyword(s):  
Dentate Gyrus ◽  
Progenitor Cells ◽  
Subventricular Zone ◽  
Adult Mouse

Effect of chronic elevated carbon dioxide on the expression of acid-base transporters in the neonatal and adult mouse

2007 ◽  
Vol 293 (3) ◽  
pp. R1294-R1302 ◽  
Author(s):  
Amjad Kanaan ◽  
Robert M. Douglas ◽  
Seth L. Alper ◽  
Walter F. Boron ◽  
Gabriel G. Haddad
Keyword(s):  
Mammalian Cells ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Mouse Heart ◽  
Ph Homeostasis ◽  
Acid Base ◽  
Adult Mice ◽  
Sodium Hydrogen Exchanger ◽  
The Face

Several pulmonary and neurological conditions, both in the newborn and adult, result in hypercapnia. This leads to disturbances in normal pH homeostasis. Most mammalian cells maintain tight control of intracellular pH (pHi) using a group of transmembrane proteins that specialize in acid-base transport. These acid-base transporters are important in adjusting pHi during acidosis arising from hypoventilation. We hypothesized that exposure to chronic hypercapnia induces changes in the expression of acid-base transporters. Neonatal and adult CD-1 mice were exposed to either 8% or 12% CO2 for 2 wk. We used Western blot analysis of membrane protein fractions from heart, kidney, and various brain regions to study the response of specific acid-base transporters to CO2. Chronic CO2 increased the expression of the sodium hydrogen exchanger 1 (NHE1) and electroneutral sodium bicarbonate cotransporter (NBCn1) in the cerebral cortex, heart, and kidney of neonatal but not adult mice. CO2 increased the expression of electrogenic NBC (NBCe1) in the neonatal but not the adult mouse heart and kidney. Hypercapnia decreased the expression of anion exchanger 3 (AE3) in both the neonatal and adult brain but increased AE3 expression in the neonatal heart. We conclude that: 1) chronic hypercapnia increases the expression of the acid extruders NHE1, NBCe1 and NBCn1 and decreases the expression of the acid loader AE3, possibly improving the capacity of the cell to maintain pHi in the face of acidosis; and 2) the heterogeneous response of tissues to hypercapnia depends on the level of CO2 and development.

scholarly journals Patterns and Dynamics of Subventricular Zone Neuroblast Migration in the Ischemic Striatum of the Adult Mouse

2009 ◽  
Vol 29 (7) ◽  
pp. 1240-1250 ◽  
Author(s):  
Rui L Zhang ◽  
Michael Chopp ◽  
Sara R Gregg ◽  
Yier Toh ◽  
Cindi Roberts ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Adult Mouse ◽  
Fluorescent Protein ◽  
Brain Slices ◽  
Time Lapse ◽  
Adult Mouse Brain ◽  
Neuroblast Migration ◽  
Multiple Processes ◽  
Migratory Routes ◽  
Green Fluorescent

The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse microscopy, we imaged migration of neuroblasts and cerebral vessels in living brain slices of adult doublecortin (DCX, a marker of neuroblasts) enhanced green fluorescent protein (eGFP) transgenic mice that were subjected to 7 days of stroke. Our results show that neuroblasts originating in the subventricular zone (SVZ) of adult mouse brain laterally migrated in chains or individually to reach the ischemic striatum. The chains were initially formed at the border between the SVZ and the striatum by neuroblasts in the SVZ and then extended to the striatum. The average speed of DCX-eGFP-expressing cells within chains was 28.67 ± 1.04 μm/h, which was significantly faster ( P < 0.01) than the speed of the cells in the SVZ (17.98 ± 0.57 μm/h). Within the ischemic striatum, individual neuroblasts actively extended or retracted their processes, suggestive of probing the immediate microenvironment. The neuroblasts close to cerebral blood vessels exhibited multiple processes. Our data suggest that neuroblasts actively interact with the microenvironment to reach the ischemic striatum by multiple migratory routes.

scholarly journals The hedgehog signaling pathway is expressed in the adult mouse hypothalamus and modulated by fasting

2021 ◽  
Author(s):  
Patrick J. Antonellis ◽  
Staci E. Engle ◽  
Kathryn M. Brewer ◽  
Nicolas F. Berbari
Keyword(s):  
Feeding Behavior ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Adult Mouse ◽  
Brain Regions ◽  
Adult Brain ◽  
Hedgehog Pathway ◽  
Transcriptional Level ◽  
Hedgehog Signaling Pathway

The importance of the primary cilium was initially highlighted by the class of human genetic disorders known as ciliopathies. Patients with ciliopathies such as Bardet-Biedl and Alstrom syndrome exhibit hyperphagia-associated obesity as a core clinical phenotype. How primary cilia contribute to energy homeostasis and feeding behavior is complex and unclear, but cilia appear important in both developmental and homeostatic processes. Primary cilia are important signaling centers, required for hedgehog signaling and localization of specific G protein-coupled receptors (GPCRs) with known roles in feeding behavior in mammals. The hedgehog pathway is best known for its role in developmental patterning, but now has recognized roles in adult tissues as well. In the postnatal brain, cilia and hedgehog signaling are important for growth and maintenance of neural progenitors, however, the role of hedgehog signaling in the differentiated adult brain is less clear. Here, we provide a detailed analysis of the expression of core components of the hedgehog signaling pathway in the adult mouse hypothalamus with an emphasis on feeding centers. We show that hedgehog pathway genes continue to be expressed in differentiated neurons important for regulation of feeding behavior. Furthermore, we demonstrate for the first time that pathway activity is regulated at the transcriptional level by fasting. These data suggest that hedgehog signaling is involved in the proper functioning of brain regions which regulate feeding behavior and that hedgehog pathway dysfunction may play a role in the obesity observed in certain ciliopathies.

scholarly journals Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice

2020 ◽  
Vol 14 ◽  
Author(s):  
Shunsuke Ikegaya ◽  
Yurika Iga ◽  
Sumiko Mikawa ◽  
Li Zhou ◽  
Manabu Abe ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Mouse Brain ◽  
Adult Mouse ◽  
Anterior Commissure ◽  
Granule Cell Layer ◽  
Subgranular Zone ◽  
Adult Mouse Brain ◽  
Chain Migration ◽  
Neurogenic Niche ◽  
Neuroblast Migration

In the adult mouse brain, neurogenesis occurs mainly in the ventricular-subventricular zone (V-SVZ) and the subgranular zone of the hippocampal dentate gyrus. Neuroblasts generated in the V-SVZ migrate to the olfactory bulb via the rostral migratory stream (RMS) in response to guidance molecules, such as netrin-1. We previously showed that the related netrin-5 (NTN5) is expressed in Mash1-positive transit-amplifying cells and doublecortin-positive neuroblasts in the granule cell layer of the olfactory bulb, the RMS, and the subgranular zone of the adult mouse brain. However, the precise role of NTN5 in adult neurogenesis has not been investigated. In this study, we show that proliferation in the neurogenic niche is impaired in NTN5 knockout mice. The number of proliferating (EdU-labeled) cells in NTN5 KO mice was significantly lower in the V-SVZ, whereas the number of Ki67-positive proliferating cells was unchanged, suggesting a longer cell cycle and decreased cell division in NTN5 KO mice. The number of EdU-labeled cells in the RMS and olfactory bulb was unchanged. By contrast, the numbers of EdU-labeled cells in the cortex, basal ganglia/lateral septal nucleus, and corpus callosum/anterior commissure were increased, which largely represented oligodendrocyte lineage cells. Lastly, we found that chain migration in the RMS of NTN5 KO mice was disorganized. These findings suggest that NTN5 may play important roles in promoting proliferation in the V-SVZ niche, organizing proper chain migration in the RMS, and suppressing oligodendrogenesis in the brain.

Oral Infectivity of Vibrio vulnificus in Suckling Mice

1987 ◽  
Vol 50 (12) ◽  
pp. 1013-1016 ◽  
Author(s):  
ANTOLIN L. REYES ◽  
CLIFFORD H. JOHNSON ◽  
PROCTER L. SPAULDING ◽  
GERARD N. STELMA
Keyword(s):  
Adult Mouse ◽  
Vibrio Vulnificus ◽  
Close Correlation ◽  
Oral Route ◽  
Environmental Isolates ◽  
Suckling Mice ◽  
Virulent Isolate ◽  
Adult Mice ◽  
Lethal Doses ◽  
Intraperitoneal Inoculation

Lethal doses of 11 clinical and environmental isolates of Vibrio vulnificus were determined in suckling mice after oral challenge. With one exception, isolates that were virulent to iron-overloaded adult mice after intraperitoneal inoculation were highly lethal to the infant mice (&gt;50% lethality at 105 CFU/mouse). The virulent isolate that failed to kill infant mice at 105 CFU had lost its invasiveness. Conditionally virulent isolates that were virulent only to simultaneously iron-overloaded and immunosuppressed adult mice required &gt; 109 CFU to kill the infant mice. Avirulent isolates failed to kill at &gt;109 CFU/mouse. There were no significant differences in the lethalities of clinical and environmental isolates. These findings demonstrated a close correlation between virulence in the iron-overloaded adult mouse and infectivity by the oral route.

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