TY  - JOUR
AU  - Weselek, Grit
AU  - Keiner, Silke
AU  - Fauser, Mareike
AU  - Wagenführ, Lisa
AU  - Müller, Julia
AU  - Kaltschmidt, Barbara
AU  - Brandt, Moritz D
AU  - Gerlach, Manfred
AU  - Redecker, Christoph
AU  - Hermann, Andreas
AU  - Storch, Alexander
TI  - Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche.
JO  - Stem cells
VL  - 38
IS  - 9
SN  - 1066-5099
CY  - Hoboken, NJ
PB  - Wiley-Blackwell
M1  - DZNE-2020-01413
SP  - 1188–1201
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Cell Proliferation: drug effects
KW  - Hippocampus: cytology
KW  - Lateral Ventricles: cytology
KW  - Mesencephalon: cytology
KW  - Mice, Inbred C57BL
KW  - Neural Stem Cells: cytology
KW  - Neural Stem Cells: drug effects
KW  - Neurogenesis: drug effects
KW  - Norepinephrine: pharmacology
KW  - Olfactory Bulb: cytology
KW  - Phenotype
KW  - Receptors, Adrenergic, beta: metabolism
KW  - Signal Transduction: drug effects
KW  - Stem Cell Niche
LB  - PUB:(DE-HGF)16
C6  - pmid:32473039
DO  - DOI:10.1002/stem.3232
UR  - https://pub.dzne.de/record/153416
ER  -