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  - Lüningschrör, Patrick
A1  - Slotta, Carsten
A1  - Heimann, Peter
A1  - Briese, Michael
A1  - Weikert, Ulrich M.
A1  - Massih, Bita
A1  - Appenzeller, Silke
A1  - Sendtner, Michael
A1  - Kaltschmidt, Christian
A1  - Kaltschmidt, Barbara
T1  - Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves
JF  - Frontiers in Cellular Neuroscience
N2  - Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4\(^+\) and CD8\(^+\) T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.
KW  - Schwann cells
KW  - autophagy
KW  - immune response
KW  - myelin
KW  - PLEKHG5
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207538
SN  - 1662-5102
VL  - 14
ER  -