scholarly journals Aging impairs the essential contributions of non‐glial progenitors to neurorepair in the dorsal telencephalon of the Killifish Nothobranchius furzeri

Aging Cell ◽  
2021 ◽  
Vol 20 (9) ◽  
Author(s):  
Jolien Van houcke ◽  
Valerie Mariën ◽  
Caroline Zandecki ◽  
Sophie Vanhunsel ◽  
Lieve Moons ◽  
...  
2021 ◽  
Author(s):  
Jolien Van houcke ◽  
Valerie Mariën ◽  
Caroline Zandecki ◽  
Sophie Vanhunsel ◽  
Lieve Moons ◽  
...  

SummaryThe aging central nervous system (CNS) of mammals displays progressive limited regenerative abilities. Recovery after loss of neurons is extremely restricted in the aged brain. Many research models fall short in recapitulating mammalian aging hallmarks or have an impractically long lifespan. We established a traumatic brain injury model in the African turquoise killifish (Nothobranchius furzeri), a regeneration-competent vertebrate model that evolved to naturally age extremely fast. Stab-wound injury of the aged killifish dorsal telencephalon unveils an impaired and incomplete regeneration response when compared to young individuals. Remarkably, killifish brain regeneration is mainly supported by atypical non-glial progenitors, yet their proliferation capacity appears declined with age. We identified a high inflammatory response and glial scarring to also underlie the hampered generation of new neurons in aged fish. These primary results will pave the way for further research to unravel the factor age in relation to neurorepair, and to improve therapeutic strategies to restore the injured and/or diseased aged mammalian CNS.HighlightsAging impairs neurorepair in the killifish pallium at multiple stages of the regeneration processAtypical non-glial progenitors support the production of new neurons in the naive and injured dorsal palliumThe impaired regeneration capacity of aged killifish is characterized by a reduced reactive proliferation of these progenitors followed by a decreased generation of newborn neurons that in addition, fail to reach the injury siteExcessive inflammation and glial scarring surface as potential brakes on brain repair in the aged killifish pallium


2021 ◽  
Author(s):  
Valerie Mariën ◽  
Jolien Van houcke ◽  
Lutgarde Arckens

This perfusion protocol is essential for preserving tissue morphology in order to perform good quality immunohistochemical stainings. Here, we show you how we perform our perfusions on the African turquoise killifish. This protocol was already used in the following publications: Aging impairs the essential contributions of non-glial progenitors to neurorepair in the dorsal telencephalon of the Killifish Nothobranchius furzeri - PubMed (nih.gov) Single-cell sequencing of the adult killifish (N. furzeri) brain identifies an atypical progenitor, glial and neuronal heterogeneity | bioRxiv


2001 ◽  
Vol 48 (2) ◽  
pp. 75-86 ◽  
Author(s):  
JoAnn M. Gensert ◽  
James E. Goldman

2012 ◽  
Vol 75 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Livia D'Angelo ◽  
Paolo de Girolamo ◽  
Alessandro Cellerino ◽  
Eva Terzibasi Tozzini ◽  
Luciana Castaldo ◽  
...  

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 101-111 ◽  
Author(s):  
M. Yoshida ◽  
Y. Suda ◽  
I. Matsuo ◽  
N. Miyamoto ◽  
N. Takeda ◽  
...  

The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty spiracles, and their expression patterns have suggested their involvement in regional patterning of the forebrain. To define their functions we introduced mutations into these loci. The newborn Emx2 mutants displayed defects in archipallium structures that are believed to play essential roles in learning, memory and behavior: the dentate gyrus was missing, and the hippocampus and medial limbic cortex were greatly reduced in size. In contrast, defects were subtle in adult Emx1 mutant brain. In the early developing Emx2 mutant forebrain, the evagination of cerebral hemispheres was reduced and the roof between the hemispheres was expanded, suggesting the lateral shift of its boundary. Defects were not apparent, however, in the region where Emx1 expression overlaps that of Emx2, nor was any defect found in the early embryonic forebrain caused by mutation of the Emx1 gene, of which expression principally occurs within the Emx2-positive region. Emx2 most likely delineates the palliochoroidal boundary in the absence of Emx1 expression during early dorsal forebrain patterning. In the more lateral region of telencephalon, Emx2-deficiency may be compensated for by Emx1 and vice versa. Phenotypes of newborn brains also suggest that these genes function in neurogenesis corresponding to their later expressions.


2009 ◽  
Vol 5 (3-4) ◽  
pp. 57-67 ◽  
Author(s):  
Konstantina Psachoulia ◽  
Francoise Jamen ◽  
Kaylene M. Young ◽  
William D. Richardson

Oligodendrocyte precursors (OLPs or ‘NG2 cells’) are abundant in the adult mouse brain, where they continue to proliferate and generate new myelinating oligodendrocytes. By cumulative BrdU labelling, we estimated the cell cycle timeTCand the proportion of NG2 cells that is actively cycling (the growth fraction) at ~ postnatal day 6 (P6), P60, P240 and P540. In the corpus callosum,TCincreased from <2 days at P6 to ~9 days at P60 to ~70 days at P240 and P540. In the cortex,TCincreased from ~2 days to >150 days over the same period. The growth fraction remained relatively invariant at ~50% in both cortex and corpus callosum – that is, similar numbers of mitotically active and inactive NG2 cells co-exist at all ages. Our data imply that a stable population of quiescent NG2 cells appears before the end of the first postnatal week and persists throughout life. The mitotically active population acts as a source of new oligodendrocytes during adulthood, while the biological significance of the quiescent population remains to be determined. We found that the mitotic status of adult NG2 cells is unrelated to their developmental site of origin in the ventral or dorsal telencephalon. We also report that new oligodendrocytes continue to be formed at a slow rate from NG2 cells even after P240 (8 months of age).


2021 ◽  
Author(s):  
Kiara Aiello ◽  
Jurgen Bolz

While it is known that Semaphorin 3C acts as a guidance cue for axons during brain development, their potential role during interneuron migration is largely unknown. One striking observation is that Sema3C demarcates the pallial/subpallial border and the intracortical pathway of cortical interneurons in the dorsal telencephalon. Moreover, migrating cortical interneurons express Neuropilin1 and Neuropilin2, described receptors for Semaphorin 3A, 3F and 3C. All these reasons prompt us to examine possible roles for Sema3C on cortical interneuron migration. Using several in vitro approaches, we showed that Nrp1-expressing MGE-derived interneurons from the deep migratory stream migrate towards the increasing Sema3C gradients. In contrast, inhibitory neurons from the superficial migratory stream that express Nrp2, do not respond to this guidance cue. In the present study, we proposed that diffusible Sema3C expressed in the Pallium provides a permissive corridor that attracts the Nrp1- expressing interneurons from the DMS into the dorsal telencephalon.


2020 ◽  
Author(s):  
Zhongfu Shen ◽  
Yang Lin ◽  
Jiajun Yang ◽  
David J. Jörg ◽  
Yuwei Peng ◽  
...  

SUMMARYRadial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted “intermediate” precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.


Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1421
Author(s):  
Valentina S. Evsiukova ◽  
Elizabeth A. Kulikova ◽  
Alexander V. Kulikov

Short-lived turquoise killifish (Nothobranchius furzeri) have become a popular model organism for neuroscience. In the present paper we study for the first time their behavior in the novel tank diving test and the levels of mRNA of various 5-HT-related genes in brains of 2-, 4- and 6-month-old males and females of N. furzeri. The marked effect of age on body mass, locomotor activity and the mRNA level of Tph1b, Tph2, Slc6a4b, Mao, Htr1aa, Htr2a, Htr3a, Htr3b, Htr4, Htr6 genes in the brains of N. furzeri males was shown. Locomotor activity and expression of the Mao gene increased, while expression of Tph1b, Tph2, Slc6a4b, Htr1aa, Htr2a, Htr3a, Htr3b, Htr4, Htr6 genes decreased in 6-month-old killifish. Significant effects of sex on body mass as well as on mRNA level of Tph1a, Tph1b, Tph2, Slc6a4b, Htr1aa, 5-HT2a, Htr3a, Htr3b, Htr4, and Htr6 genes were revealed: in general both the body mass and the expression of these genes were higher in males. N. furzeri is a suitable model with which to study the fundamental problems of age-related alterations in various mRNA levels related with the brains 5-HT system.


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