Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice

Norepinephrine (NE), and specific adrenoceptors, have been reported to influence distinct aspects of adult hippocampal neurogenesis, including latent stem cell activation, progenitor proliferation, and differentiation. These findings are predominantly based on the use of pharmacological approaches i...

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Main Authors: Darshana Kapri, Krishna C. Vadodaria, Karen S. Rommelfanger, Yvonne E. Ogbonmwan, L. Cameron Liles, Kimberly A. Fernandes-Thomas, Sonali S. Salvi, Basma F.A. Husain, David Weinshenker, Vidita A. Vaidya
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:IBRO Neuroscience Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667242122000835
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author Darshana Kapri
Krishna C. Vadodaria
Karen S. Rommelfanger
Yvonne E. Ogbonmwan
L. Cameron Liles
Kimberly A. Fernandes-Thomas
Sonali S. Salvi
Basma F.A. Husain
David Weinshenker
Vidita A. Vaidya
author_facet Darshana Kapri
Krishna C. Vadodaria
Karen S. Rommelfanger
Yvonne E. Ogbonmwan
L. Cameron Liles
Kimberly A. Fernandes-Thomas
Sonali S. Salvi
Basma F.A. Husain
David Weinshenker
Vidita A. Vaidya
author_sort Darshana Kapri
collection DOAJ
description Norepinephrine (NE), and specific adrenoceptors, have been reported to influence distinct aspects of adult hippocampal neurogenesis, including latent stem cell activation, progenitor proliferation, and differentiation. These findings are predominantly based on the use of pharmacological approaches in both in vitro and in vivo systems. Here, we sought to assess the consequences of genetic ablation of NE on adult hippocampal neurogenesis, by examining dopamine β hydroxylase knockout (Dbh -/-) mice, which lack NE from birth. We find that Dbh -/- mice exhibit no difference in adult hippocampal progenitor proliferation and survival. Further, the number of immature newborn neurons, labeled using stage-specific developmental markers within the hippocampal neurogenic niche, was also unaltered in Dbh -/- mice. In contrast, the noradrenergic neurotoxin DSP-4, which had previously been shown to reduce adult hippocampal neurogenesis in rats, also resulted in a decline in hippocampal progenitor proliferation in C57/Bl6N mice. These findings indicate that pharmacological lesioning of noradrenergic afferents in adulthood, but not the complete genetic loss of NE from birth, impairs adult hippocampal neurogenesis in mice.
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spelling doaj.art-384b53d4283246fbbb35144e26820ae12022-12-22T03:01:23ZengElsevierIBRO Neuroscience Reports2667-24212022-12-0113420425Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient miceDarshana Kapri0Krishna C. Vadodaria1Karen S. Rommelfanger2Yvonne E. Ogbonmwan3L. Cameron Liles4Kimberly A. Fernandes-Thomas5Sonali S. Salvi6Basma F.A. Husain7David Weinshenker8Vidita A. Vaidya9Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, IndiaDepartment of Human Genetics, Emory University, Atlanta, GA 30322, USADepartment of Human Genetics, Emory University, Atlanta, GA 30322, USADepartment of Human Genetics, Emory University, Atlanta, GA 30322, USADepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, IndiaDepartment of Human Genetics, Emory University, Atlanta, GA 30322, USA; Correspondence to: Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Whitehead 301, Atlanta, GA 30322, USA.Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India; Correspondence to: Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mumbai 400005, India.Norepinephrine (NE), and specific adrenoceptors, have been reported to influence distinct aspects of adult hippocampal neurogenesis, including latent stem cell activation, progenitor proliferation, and differentiation. These findings are predominantly based on the use of pharmacological approaches in both in vitro and in vivo systems. Here, we sought to assess the consequences of genetic ablation of NE on adult hippocampal neurogenesis, by examining dopamine β hydroxylase knockout (Dbh -/-) mice, which lack NE from birth. We find that Dbh -/- mice exhibit no difference in adult hippocampal progenitor proliferation and survival. Further, the number of immature newborn neurons, labeled using stage-specific developmental markers within the hippocampal neurogenic niche, was also unaltered in Dbh -/- mice. In contrast, the noradrenergic neurotoxin DSP-4, which had previously been shown to reduce adult hippocampal neurogenesis in rats, also resulted in a decline in hippocampal progenitor proliferation in C57/Bl6N mice. These findings indicate that pharmacological lesioning of noradrenergic afferents in adulthood, but not the complete genetic loss of NE from birth, impairs adult hippocampal neurogenesis in mice.http://www.sciencedirect.com/science/article/pii/S2667242122000835DSP-4Dbh knockout miceDoublecortinBrdUHippocampal progenitorProliferation
spellingShingle Darshana Kapri
Krishna C. Vadodaria
Karen S. Rommelfanger
Yvonne E. Ogbonmwan
L. Cameron Liles
Kimberly A. Fernandes-Thomas
Sonali S. Salvi
Basma F.A. Husain
David Weinshenker
Vidita A. Vaidya
Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
IBRO Neuroscience Reports
DSP-4
Dbh knockout mice
Doublecortin
BrdU
Hippocampal progenitor
Proliferation
title Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
title_full Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
title_fullStr Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
title_full_unstemmed Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
title_short Genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta-hydroxylase deficient mice
title_sort genetic loss of norepinephrine does not alter adult hippocampal neurogenesis in dopamine beta hydroxylase deficient mice
topic DSP-4
Dbh knockout mice
Doublecortin
BrdU
Hippocampal progenitor
Proliferation
url http://www.sciencedirect.com/science/article/pii/S2667242122000835
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