TY  - JOUR
A1  - Weselek, Grit
A1  - Keiner, Silke
A1  - Fauser, Mareike
A1  - Wagenführ, Lisa
A1  - Müller, Julia
A1  - Kaltschmidt, Barbara
A1  - Brandt, Moritz D.
A1  - Gerlach, Manfred
A1  - Redecker, Christoph
A1  - Hermann, Andreas
A1  - Storch, Alexander
T1  - Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche
JF  - Stem Cells
N2  - 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  - adult neurogenesis
KW  - hippocampus
KW  - noradrenaline
KW  - norepinephrine
KW  - olfactory bulb neurogenesis
KW  - subventricular zone
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218250
VL  - 38
IS  - 9
SP  - 1188
EP  - 1201
ER  - 
TY  - JOUR
A1  - Fauser, Mareike
A1  - Weselek, Grit
A1  - Hauptmann, Christine
A1  - Markert, Franz
A1  - Gerlach, Manfred
A1  - Hermann, Andreas
A1  - Storch, Alexander
T1  - Catecholaminergic Innervation of Periventricular Neurogenic Regions of the Developing Mouse Brain
JF  - Frontiers in Neuroanatomy
N2  - The major catecholamines—dopamine (DA) and norepinephrine (NE)—are not only involved in synaptic communication but also act as important trophic factors and might ultimately be involved in mammalian brain development. The catecholaminergic innervation of neurogenic regions of the developing brain and its putative relationship to neurogenesis is thus of pivotal interest. We here determined DA and NE innervation around the ventricular/subventricular zone (VZ/SVZ) bordering the whole ventricular system of the developing mouse brain from embryonic day 14.5 (E14.5), E16.5, and E19.5 until postnatal day zero (P0) by histological evaluation and HPLC with electrochemical detection. We correlated these data with the proliferation capacity of the respective regions by quantification of MCM\(^{2+}\) cells. During development, VZ/SVZ catecholamine levels dramatically increased between E16.5 and P0 with DA levels increasing in forebrain VZ/SVZ bordering the lateral ventricles and NE levels raising in midbrain/hindbrain VZ/SVZ bordering the third ventricle, the aqueduct, and the fourth ventricle. Conversely, proliferating MCM\(^{2+}\) cell counts dropped between E16.5 and E19.5 with a special focus on all VZ/SVZs outside the lateral ventricles. We detected an inverse strong negative correlation of the proliferation capacity in the periventricular neurogenic regions (log-transformed MCM\(^{2+}\) cell counts) with their NE levels (r = −0.932; p < 0.001), but not their DA levels (r = 0.440; p = 0.051) suggesting putative inhibitory effects of NE on cell proliferation within the periventricular regions during mouse brain development. Our data provide the first framework for further demandable studies on the functional importance of catecholamines, particularly NE, in regulating neural stem/progenitor cell proliferation and differentiation during mammalian brain development.
KW  - brain development
KW  - ventricular zone
KW  - catecholamines
KW  - norepinephrine
KW  - dopamine
KW  - neurogenesis
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212485
VL  - 14
ER  -