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000153416 0247_ $$2doi$$a10.1002/stem.3232
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000153416 041__ $$aEnglish
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000153416 1001_ $$0P:(DE-2719)9001489$$aWeselek, Grit$$b0$$udzne
000153416 245__ $$aNorepinephrine is a negative regulator of the adult periventricular neural stem cell niche.
000153416 260__ $$aHoboken, NJ$$bWiley-Blackwell$$c2020
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000153416 520__ $$aThe 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.
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000153416 650_2 $$2MeSH$$aAnimals
000153416 650_2 $$2MeSH$$aCell Proliferation: drug effects
000153416 650_2 $$2MeSH$$aHippocampus: cytology
000153416 650_2 $$2MeSH$$aLateral Ventricles: cytology
000153416 650_2 $$2MeSH$$aMesencephalon: cytology
000153416 650_2 $$2MeSH$$aMice, Inbred C57BL
000153416 650_2 $$2MeSH$$aNeural Stem Cells: cytology
000153416 650_2 $$2MeSH$$aNeural Stem Cells: drug effects
000153416 650_2 $$2MeSH$$aNeurogenesis: drug effects
000153416 650_2 $$2MeSH$$aNorepinephrine: pharmacology
000153416 650_2 $$2MeSH$$aOlfactory Bulb: cytology
000153416 650_2 $$2MeSH$$aPhenotype
000153416 650_2 $$2MeSH$$aReceptors, Adrenergic, beta: metabolism
000153416 650_2 $$2MeSH$$aSignal Transduction: drug effects
000153416 650_2 $$2MeSH$$aStem Cell Niche
000153416 7001_ $$aKeiner, Silke$$b1
000153416 7001_ $$0P:(DE-HGF)0$$aFauser, Mareike$$b2
000153416 7001_ $$aWagenführ, Lisa$$b3
000153416 7001_ $$aMüller, Julia$$b4
000153416 7001_ $$aKaltschmidt, Barbara$$b5
000153416 7001_ $$0P:(DE-HGF)0$$aBrandt, Moritz D$$b6
000153416 7001_ $$aGerlach, Manfred$$b7
000153416 7001_ $$aRedecker, Christoph$$b8
000153416 7001_ $$0P:(DE-HGF)0$$aHermann, Andreas$$b9
000153416 7001_ $$0P:(DE-2719)9000306$$aStorch, Alexander$$b10$$eLast author
000153416 773__ $$0PERI:(DE-600)2030643-X$$a10.1002/stem.3232$$gVol. 38, no. 9$$n9$$p1188–1201$$tStem cells$$v38$$x1066-5099$$y2020
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