You are hereSeptember 14, 2020 | Neural Stem Cells
Norepinephrine - A New Niche-specific Regulator of Adult Neurogenesis
Review of "Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche" from STEM CELLS by Stuart P. Atkinson
Recent studies, including those from the laboratory of Alexander Storch (University of Rostock, Rostock, Germany) published in STEM CELLS, have highlighted the existence of cell‐extrinsic factors that restrict the proliferation of neural progenitor cells (NPCs) depending on the location of the associated periventricular germinal niche within the adult mammalian brain [1-3]. Related research has also suggested the implication of neurotransmitters in the control of adult NPC proliferation ; as an example, norepinephrine modulates the function of the hippocampal stem cell niche . Now, the Storch team returns with a new STEM CELLS article  in which they describe their exploration of norepinephrine as a regulator of adult NPC proliferation within the periventricular regions of the adult mouse brain.
Histological and neurochemical analyses undertaken by Weselek et al. revealed a reduced in vivo NPC proliferation rate upon the increased norepinephrine-mediated innervation of the adult periventricular germinal niches. Specifically, the low levels of norepinephrine in the subventricular zone prompted high NPC proliferation, whereas the high levels of norepinephrine in the hypothalamic and midbrain periventricular germinal niches promoted a reduction in NPC proliferation, most likely mediated through the direct stimulation of β-adrenergic receptor signaling .
Importantly, adrenergic receptor signaling can also boost adult hippocampal neurogenesis, and the authors of this study found that norepinephrine enhanced adult neurogenesis in the dentate gyrus of the hippocampus, suggesting the neurogenic niche-dependent function of norepinephrine.
The authors further strengthened the association of norepinephrine and decreased NPC proliferation by demonstrating how the intraventricular infusion of norepinephrine decreased NPC proliferation and neurogenesis in the subventricular zone‐olfactory bulb system, and how the pharmacological inhibition of norepinephrine increased NPC proliferation and early neurogenesis in the caudal periventricular germinal niches. Finally, the increase in NPC proliferation following the ablation of norepinephrine neurons with a neurotoxin further bolstered the author's findings.
Overall, this exciting study now highlights the neurotransmitter norepinephrine as a negative regulator of NPC niches and a crucial regulator of adult neurogenesis. Furthermore, the authors anticipate that their findings will pave the way towards the development of new therapeutics to influence neurogenesis in hypothalamus‐related metabolic diseases such as obesity or type 2 diabetes  or stimulate endogenous midbrain regeneration  in neurodegenerative processes such as Parkinson's disease.
For more on those factors controlling the niche-specific proliferation of NPCs, stay tuned to the Stem Cells Portal!
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- Weselek G, Keiner S, Fauser M, et al., Norepinephrine is a negative regulator of the adult periventricular neural stem cell niche. STEM CELLS 2020;38:1188-1201.
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