PT  - JOURNAL ARTICLE
AU  - Manveen K. Gupta
AU  - Robert S. Papay
AU  - Chris W. D. Jurgens
AU  - Robert J. Gaivin
AU  - Ting Shi
AU  - Van A. Doze
AU  - Dianne M. Perez
TI  - α<sub>1</sub>-Adrenergic Receptors Regulate Neurogenesis and Gliogenesis
AID  - 10.1124/mol.109.057307
DP  - 2009 Aug 01
TA  - Molecular Pharmacology
PG  - 314--326
VI  - 76
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/76/2/314.short
4100  - http://molpharm.aspetjournals.org/content/76/2/314.full
SO  - Mol Pharmacol2009 Aug 01; 76
AB  - The understanding of the function of α1-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 α1-adrenergic receptor subtypes in tissues in which they are normally expressed. We identified intriguing α1A-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 α1A-adrenergic receptor transgenic mice or normal mice given the α1A-adrenergic receptor-selective agonist, cirazoline. Neonatal neurospheres isolated from normal mice expressed a mixture of α1-adrenergic receptor subtypes, and stimulation of these receptors resulted in increased expression of the α1B-adrenergic receptor subtype, proneural basic helix-loop-helix transcription factors, and the differentiation and migration of neuronal progenitors for catecholaminergic neurons and interneurons. α1-Adrenergic receptor stimulation increased the apoptosis of astrocytes and regulated survival of neonatal neurons through phosphatidylinositol 3-kinase signaling. However, in adult normal neurospheres, α1-adrenergic receptor stimulation increased the expression of glial markers at the expense of neuronal differentiation. In vivo, S100-positive glial and βIII tubulin neuronal progenitors colocalized with either α1-adrenergic receptor subtype in the olfactory bulb. Our results indicate that α1-adrenergic receptors can regulate both neurogenesis and gliogenesis that may be developmentally dependent. Our findings may lead to new therapies to treat neurodegenerative diseases.