Journal Article

DZNE-2020-01413

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche.

Weselek, G.DZNE* ; Keiner, S. ; Fauser, M. ; Wagenführ, L. ; Müller, J. ; Kaltschmidt, B. ; Brandt, M. D. ; Gerlach, M. ; Redecker, C. ; Hermann, A. ; Storch, A. (Last author)DZNE*

2020
Wiley-Blackwell Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/stem.3232

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.

Keyword(s): Animals (MeSH) ; Cell Proliferation: drug effects (MeSH) ; Hippocampus: cytology (MeSH) ; Lateral Ventricles: cytology (MeSH) ; Mesencephalon: cytology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Neural Stem Cells: drug effects (MeSH) ; Neurogenesis: drug effects (MeSH) ; Norepinephrine: pharmacology (MeSH) ; Olfactory Bulb: cytology (MeSH) ; Phenotype (MeSH) ; Receptors, Adrenergic, beta: metabolism (MeSH) ; Signal Transduction: drug effects (MeSH) ; Stem Cell Niche (MeSH)

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Contributing Institute(s):

1. Non-Motor Symptoms in Parkinson's disease (AG Storch)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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