You are here

| 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 [4]; as an example, norepinephrine modulates the function of the hippocampal stem cell niche [5]. Now, the Storch team returns with a new STEM CELLS article [6] 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 [7]. 

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 [8] or stimulate endogenous midbrain regeneration [9] 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!

References

  1. Golmohammadi MG, Blackmore DG, Large B, et al., Comparative Analysis of the Frequency and Distribution of Stem and Progenitor Cells in the Adult Mouse Brain. STEM CELLS 2008;26:979-987.
  2. Hermann A, Suess C, Fauser M, et al., Rostro-Caudal Gradual Loss of Cellular Diversity Within the Periventricular Regions of the Ventricular System. STEM CELLS 2009;27:928-941.
  3. Hermann A, Maisel M, Wegner F, et al., Multipotent Neural Stem Cells from the Adult Tegmentum with Dopaminergic Potential Develop Essential Properties of Functional Neurons. STEM CELLS 2006;24:949-964.
  4. Young SZ, Taylor MM, and Bordey A, Neurotransmitters couple brain activity to subventricular zone neurogenesis. European Journal of Neuroscience 2011;33:1123-1132.
  5. Kulkarni VA, Jha S, and Vaidya VA, Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus. European Journal of Neuroscience 2002;16:2008-2012.
  6. 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.
  7. Jhaveri DJ, Nanavaty I, Prosper BW, et al., Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis. PLOS ONE 2014;9:e98736.
  8. Recabal A, Caprile T, and García-Robles MdlA, Hypothalamic Neurogenesis as an Adaptive Metabolic Mechanism. Frontiers in Neuroscience 2017;11:190.
  9. Hermann A and Storch A, Endogenous Regeneration in Parkinson's Disease: Do We Need Orthotopic Dopaminergic Neurogenesis? STEM CELLS 2008;26:2749-2752.