title: Opposing effects of α2- and β-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.
abstract: Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Dhanisha J
authors.initials: DJ
authors.lastname: Jhaveri
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Ishira
authors.initials: I
authors.lastname: Nanavaty
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Prosper
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Swanand
authors.initials: S
authors.lastname: Marathe
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Basma F A
authors.initials: BF
authors.lastname: Husain
authors.affiliation: Departments of Pediatrics and Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kernie
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors.forename: Vidita A
authors.initials: VA
authors.lastname: Vaidya
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D064231:Nestin