Document Detail


alpha1-Adrenergic receptors regulate neurogenesis and gliogenesis.
MedLine Citation:
PMID:  19487244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The understanding of the function of alpha(1)-adrenergic receptors in the brain has been limited due to a lack of specific ligands and antibodies. We circumvented this problem by using transgenic mice engineered to overexpress either wild-type receptor tagged with enhanced green fluorescent protein or constitutively active mutant alpha(1)-adrenergic receptor subtypes in tissues in which they are normally expressed. We identified intriguing alpha(1A)-adrenergic receptor subtype-expressing cells with a migratory morphology in the adult subventricular zone that coexpressed markers of neural stem cell and/or progenitors. Incorporation of 5-bromo-2-deoxyuridine in vivo increased in neurogenic areas in adult alpha(1A)-adrenergic receptor transgenic mice or normal mice given the alpha(1A)-adrenergic receptor-selective agonist, cirazoline. Neonatal neurospheres isolated from normal mice expressed a mixture of alpha(1)-adrenergic receptor subtypes, and stimulation of these receptors resulted in increased expression of the alpha(1B)-adrenergic receptor subtype, proneural basic helix-loop-helix transcription factors, and the differentiation and migration of neuronal progenitors for catecholaminergic neurons and interneurons. alpha(1)-Adrenergic receptor stimulation increased the apoptosis of astrocytes and regulated survival of neonatal neurons through phosphatidylinositol 3-kinase signaling. However, in adult normal neurospheres, alpha(1)-adrenergic receptor stimulation increased the expression of glial markers at the expense of neuronal differentiation. In vivo, S100-positive glial and betaIII tubulin neuronal progenitors colocalized with either alpha(1)-adrenergic receptor subtype in the olfactory bulb. Our results indicate that alpha(1)-adrenergic receptors can regulate both neurogenesis and gliogenesis that may be developmentally dependent. Our findings may lead to new therapies to treat neurodegenerative diseases.
Authors:
Manveen K Gupta; Robert S Papay; Chris W D Jurgens; Robert J Gaivin; Ting Shi; Van A Doze; Dianne M Perez
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-06-01
Journal Detail:
Title:  Molecular pharmacology     Volume:  76     ISSN:  1521-0111     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-21     Completed Date:  2009-08-17     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  314-26     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-1 Receptor Agonists
Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Biological Markers / metabolism
Cell Differentiation / genetics,  physiology
Cell Movement / genetics,  physiology
Green Fluorescent Proteins / metabolism
Imidazoles / pharmacology
Immunohistochemistry
Interneurons / cytology,  metabolism
Mice
Mice, Transgenic
Neurogenesis*
Neuroglia / metabolism*
Neurons / cytology,  drug effects,  metabolism*
Phosphatidylinositol 3-Kinases / metabolism
Receptors, Adrenergic, alpha-1 / genetics,  metabolism*
Spheroids, Cellular / metabolism
Grant Support
ID/Acronym/Agency:
5-R01-HL61438/HL/NHLBI NIH HHS; P20-RR016741/RR/NCRR NIH HHS; R01 HL098279/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adra1a protein, mouse; 0/Adrenergic alpha-1 Receptor Agonists; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Biological Markers; 0/Imidazoles; 0/Receptors, Adrenergic, alpha-1; 147336-22-9/Green Fluorescent Proteins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; QK318GVY3Y/cirazoline
Comments/Corrections

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