Faculty Opinions recommendation of Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin 1.

AbstractReactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53M/M mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53M/M zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.

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Development of the Neuro-Immune-Vascular Plexus in the Ventricular Zone of the Prenatal Rat Neocortex

Cerebral Cortex ◽

10.1093/cercor/bhaa351 ◽

2020 ◽

Author(s):

Elisa Penna ◽

Jon M Mangum ◽

Hunter Shepherd ◽

Veronica Martínez-Cerdeño ◽

Stephen C Noctor

Keyword(s):

Cerebral Cortex ◽

Ventricular Zone ◽

Cortical Development ◽

Neural Precursor Cells ◽

Neurodevelopmental Outcomes ◽

Vascular Plexus ◽

Functional Roles ◽

Rat Neocortex ◽

Cell Processes ◽

Temporal And Spatial

Abstract Microglial cells make extensive contacts with neural precursor cells (NPCs) and affiliate with vasculature in the developing cerebral cortex. But how vasculature contributes to cortical histogenesis is not yet fully understood. To better understand functional roles of developing vasculature in the embryonic rat cerebral cortex, we investigated the temporal and spatial relationships between vessels, microglia, and NPCs in the ventricular zone. Our results show that endothelial cells in developing cortical vessels extend numerous fine processes that directly contact mitotic NPCs and microglia; that these processes protrude from vessel walls and are distinct from tip cell processes; and that microglia, NPCs, and vessels are highly interconnected near the ventricle. These findings demonstrate the complex environment in which NPCs are embedded in cortical proliferative zones and suggest that developing vasculature represents a source of signaling with the potential to broadly influence cortical development. In summary, cortical histogenesis arises from the interplay among NPCs, microglia, and developing vasculature. Thus, factors that impinge on any single component have the potential to change the trajectory of cortical development and increase susceptibility for altered neurodevelopmental outcomes.

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Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

Translational Psychiatry ◽

10.1038/s41398-021-01205-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Serena Banu Gumusoglu ◽

Akanksha Sri Satya Chilukuri ◽

Benjamin Wen Qing Hing ◽

Sabrina Marie Scroggins ◽

Sreelekha Kundu ◽

...

Keyword(s):

Arginine Vasopressin ◽

Ventricular Zone ◽

Vessel Diameter ◽

Female Offspring ◽

Cell Number ◽

Differentially Expressed ◽

Adult Males ◽

Social Approach ◽

Caudate Putamen ◽

Underlying Mechanisms

AbstractPreeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring were behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically and by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior and social approach while adult females exhibited impaired procedural learning. Adult AVP-exposed males had reduced total neocortical volume. Adult AVP-exposed females had increased caudate–putamen volume, increased caudate–putamen cell number, and decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, and CA3. At postnatal day 7 (P7), AVP-exposed male and female offspring both had smaller neocortex. At P7, AVP-exposed males also had smaller caudate–putamen volume, while females had increased caudate–putamen volume relative to neocortical size. Similar to P7, E18 AVP-exposed offspring had smaller dorsal forebrain, mainly in reduced intermediate, subventricular, and ventricular zone volume, particularly in males. Decreased volume was not accounted for by cell size or cerebrovascular vessel diameter changes. E18 cortical RNAseq revealed 49 differentially-expressed genes in male AVP-exposed offspring, over-representing cytoplasmic translation processes. In females, 31 genes were differentially-expressed, over-representing collagen-related and epithelial regulation pathways. Gene expression changes in E18 AVP-exposed placenta indicated potential underlying mechanisms. Deficits in behavior and forebrain development in this AVP-based preeclampsia model were distinctly different in males and females, implicating different neurobiological bases.

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Cu2+ inhibition of glycine-activated currents in rat sacral dorsal commissural neurons

Neuroscience Letters ◽

10.1016/s0304-3940(02)00498-6 ◽

2002 ◽

Vol 328 (2) ◽

pp. 117-120 ◽

Cited By ~ 5

Author(s):

Dian-Shi Wang ◽

Hai-Lei Zhu ◽

Zhen Hong ◽

Ji-Shuo Li

Keyword(s):

Commissural Neurons

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The induction of multiple cell cycle events precedes target-related neuronal death

Development ◽

10.1242/dev.121.8.2385 ◽

1995 ◽

Vol 121 (8) ◽

pp. 2385-2395 ◽

Cited By ~ 1

Author(s):

K. Herrup ◽

J.C. Busser

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Purkinje Cell ◽

Inferior Olive ◽

Granule Cells ◽

Cerebellar Granule Cells ◽

Ventricular Zone ◽

Nuclear Antigen ◽

Electron Microscopic ◽

Related Cell

Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers--cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation--are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control.

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Presenilin-1 regulates neuronal differentiation during neurogenesis

Development ◽

10.1242/dev.127.12.2593 ◽

2000 ◽

Vol 127 (12) ◽

pp. 2593-2606 ◽

Cited By ~ 1

Author(s):

M. Handler ◽

X. Yang ◽

J. Shen

Keyword(s):

Cell Death ◽

Progenitor Cells ◽

Neuronal Differentiation ◽

Cell Fate ◽

Neural Progenitor Cells ◽

Apoptotic Cell ◽

Ventricular Zone ◽

Neural Progenitor ◽

Apoptotic Cell Death ◽

Presenilin 1

Mutations in Presenilin-1 (PS1) are a major cause of familial Alzheimer's disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(−/−) mice, suggesting that the reduction in the neural progenitor cells observed in the PS1(−/−) brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1(−/−) brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1(−/−) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(−/−) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288–292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.

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Co-release and interaction of two inhibitory co-transmitters in rat sacral dorsal commissural neurons

Neuroreport ◽

10.1097/00001756-200205240-00016 ◽

2002 ◽

Vol 13 (7) ◽

pp. 977-981 ◽

Cited By ~ 23

Author(s):

Long-Jun Wu ◽

Yong Li ◽

Tian-Le Xu

Keyword(s):

Commissural Neurons

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