scholarly journals Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tamar Licht ◽  
Esther Sasson ◽  
Batia Bell ◽  
Myriam Grunewald ◽  
Saran Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Chemotherapeutic Agent ◽  
Direct Access ◽  
Fluorescent Tracer ◽  
Cellular Processes ◽  
Membrane Contact ◽  
Endothelial Basement Membrane ◽  
Cytoplasmic Processes ◽  
Hippocampal Neural Stem Cells

Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG(have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30 nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.

scholarly journals Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes

2019 ◽  
Author(s):  
Tamar Licht ◽  
Eli Keshet
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Chemotherapeutic Agent ◽  
Direct Access ◽  
Fluorescent Tracer ◽  
Cellular Processes ◽  
Membrane Contact ◽  
Endothelial Basement Membrane ◽  
Cytoplasmic Processes ◽  
Hippocampal Neural Stem Cells

SummaryBlood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG) have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs in defiance of an intact blood-brain barrier (BBB). BBB-impermeable fluorescent tracer injected transcardially is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in areas devoid of the endothelial basement membrane. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are ‘sensed’ by NSCs.

scholarly journals Author response: Hippocampal neural stem cells facilitate access from circulation via apical cytoplasmic processes

2020 ◽  
Author(s):  
Tamar Licht ◽  
Esther Sasson ◽  
Batia Bell ◽  
Myriam Grunewald ◽  
Saran Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Author Response ◽  
Cytoplasmic Processes ◽  
Hippocampal Neural Stem Cells

scholarly journals ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence

2020 ◽  
Author(s):  
Vijay S. Adusumilli ◽  
Tara L. Walker ◽  
Rupert W. Overall ◽  
Gesa M. Klatt ◽  
Salma A. Zeidan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Functional States ◽  
Activity Dependent ◽  
Hippocampal Neural Stem Cells

scholarly journals Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain

2019 ◽  
Vol 25 (7) ◽  
pp. 1382-1405 ◽  
Author(s):  
M. Schouten ◽  
P. Bielefeld ◽  
L. Garcia-Corzo ◽  
E. M. J. Passchier ◽  
S. Gradari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Aging Brain ◽  
Hippocampal Neural Stem Cells

scholarly journals Ghrelin gene products rescue cultured adult rat hippocampal neural stem cells from high glucose insult

2016 ◽  
Vol 57 (3) ◽  
pp. 171-184 ◽  
Author(s):  
Sehee Kim ◽  
Chanyang Kim ◽  
Seungjoon Park
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
High Glucose ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Gene Products ◽  
Growth Hormone Secretagogue ◽  
Phosphohistone H3 ◽  
Ghrelin Gene ◽  
Hippocampal Neural Stem Cells

Adult hippocampal neurogenesis is decreased in type 2 diabetes, and this impairment appears to be important in cognitive dysfunction. Previous studies suggest that ghrelin gene products (acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (OB)) promote neurogenesis. Therefore, we hypothesize that ghrelin gene products may reduce the harmful effects of high glucose (HG) on hippocampal neural stem cells (NSCs). The aim of this study was to investigate the role of these peptides on the survival of cultured hippocampal NSCs exposed to HG insult. Treatment of hippocampal NSCs with AG, UAG or OB inhibited HG-induced cell death and apoptosis. Exposure of cells to the growth hormone secretagogue receptor 1a antagonist abolished the protective effects of AG against HG toxicity, whereas those of UAG or OB were preserved. All three peptides attenuated HG-induced decrease in BrdU-labeled and phosphohistone-H3-labeled cells. We also investigated the effects of ghrelin gene products on the regulation of apoptosis at the mitochondrial level. AG, UAG or OB rescued hippocampal NSCs from HG insult by inhibiting intracellular and mitochondrial reactive oxygen species generation and stabilizing mitochondrial transmembrane potential. In addition, cells treated with ghrelin gene products showed an increased Bcl-2 and decreased Bax levels, thereby increasing the Bcl-2/Bax ratio, inhibiting cytochrome c release and preventing caspase-3 activation. Finally, AG-, UAG- or OB-mediated protection was dependent on the activities of adenosine monophosphate-activated protein kinase/uncoupling protein 2 pathway. Our data indicate that ghrelin gene products may act as survival factors that preserve mitochondrial function and inhibit oxidative stress-induced apoptosis.

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