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@ARTICLE{Weselek:153416,
author = {Weselek, Grit and Keiner, Silke and Fauser, Mareike and
Wagenführ, Lisa and Müller, Julia and Kaltschmidt, Barbara
and Brandt, Moritz D and Gerlach, Manfred and Redecker,
Christoph and Hermann, Andreas and Storch, Alexander},
title = {{N}orepinephrine is a negative regulator of the adult
periventricular neural stem cell niche.},
journal = {Stem cells},
volume = {38},
number = {9},
issn = {1066-5099},
address = {Hoboken, NJ},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2020-01413},
pages = {1188–1201},
year = {2020},
abstract = {The limited proliferative capacity of neuroprogenitor cells
(NPCs) within the periventricular germinal niches (PGNs)
located caudal of the subventricular zone (SVZ) of the
lateral ventricles together with their high proliferation
capacity after isolation strongly implicates cell-extrinsic
humoral factors restricting NPC proliferation in the
hypothalamic and midbrain PGNs. We comparatively examined
the effects of norepinephrine (NE) as an endogenous
candidate regulator of PGN neurogenesis in the SVZ as well
as the periventricular hypothalamus and the periaqueductal
midbrain. Histological and neurochemical analyses revealed
that the pattern of NE innervation of the adult PGNs is
inversely associated with their in vivo NPC proliferation
capacity with low NE levels coupled to high NPC
proliferation in the SVZ but high NE levels coupled to low
NPC proliferation in hypothalamic and midbrain PGNs.
Intraventricular infusion of NE decreased NPC proliferation
and neurogenesis in the SVZ-olfactory bulb system, while
pharmacological NE inhibition increased NPC proliferation
and early neurogenesis events in the caudal PGNs. Neurotoxic
ablation of NE neurons using the Dsp4-fluoxetine protocol
confirmed its inhibitory effects on NPC proliferation.
Contrarily, NE depletion largely impairs NPC proliferation
within the hippocampus in the same animals. Our data
indicate that norepinephrine has opposite effects on the two
fundamental neurogenic niches of the adult brain with
norepinephrine being a negative regulator of adult
periventricular neurogenesis. This knowledge might
ultimately lead to new therapeutic approaches to influence
neurogenesis in hypothalamus-related metabolic diseases or
to stimulate endogenous regenerative potential in
neurodegenerative processes such as Parkinson's disease.},
keywords = {Animals / Cell Proliferation: drug effects / Hippocampus:
cytology / Lateral Ventricles: cytology / Mesencephalon:
cytology / Mice, Inbred C57BL / Neural Stem Cells: cytology
/ Neural Stem Cells: drug effects / Neurogenesis: drug
effects / Norepinephrine: pharmacology / Olfactory Bulb:
cytology / Phenotype / Receptors, Adrenergic, beta:
metabolism / Signal Transduction: drug effects / Stem Cell
Niche},
cin = {AG Storch},
ddc = {610},
cid = {I:(DE-2719)5000014},
pnm = {344 - Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32473039},
doi = {10.1002/stem.3232},
url = {https://pub.dzne.de/record/153416},
}