title: Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors.
abstract: alpha(1)-Adrenergic receptors (ARs) are not well defined in the central nervous system. The particular cell types and areas that express these receptors are uncertain because of the lack of high avidity antibodies and selective ligands. We have developed transgenic mice that either systemically overexpress the human alpha(1A)-AR subtype fused with the enhanced green fluorescent protein (EGFP) or express the EGFP protein alone under the control of the mouse alpha(1A)-AR promoter. We confirm our transgenic model against the alpha(1A)-AR knockout mouse, which expresses the LacZ gene in place of the coding region for the alpha(1A)-AR. By using these models, we have now determined cellular localization of the alpha(1A)-AR in the brain, at the protein level. The alpha(1A)-AR or the EGFP protein is expressed prominently in neuronal cells in the cerebral cortex, hippocampus, hypothalamus, midbrain, pontine olivary nuclei, trigeminal nuclei, cerebellum, and spinal cord. The types of neurons were diverse, and the alpha(1A)-AR colocalized with markers for glutamic acid decarboxylase (GAD), gamma-aminobutyric acid (GABA), and N-methyl-D-aspartate (NMDA) receptors. Recordings from alpha(1A)-AR EGFP-expressing cells in the stratum oriens of the hippocampal CA1 region confirmed that these cells were interneurons. We could not detect expression of the alpha(1A)-AR in mature astrocytes, oligodendrocytes, or cerebral blood vessels, but we could detect the alpha(1A)-AR in oligodendrocyte progenitors. We conclude that the alpha(1A)-AR is abundant in the brain, expressed in various types of neurons, and may regulate the function of oligodendrocyte progenitors, interneurons, GABA, and NMDA receptor containing neurons.
authors.affiliation: Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Papay
authors.forename: Robert
authors.initials: R
authors.lastname: Gaivin
authors.forename: Archana
authors.initials: A
authors.lastname: Jha
authors.forename: Dan F
authors.initials: DF
authors.lastname: McCune
authors.forename: John C
authors.initials: JC
authors.lastname: McGrath
authors.forename: Manoj C
authors.initials: MC
authors.lastname: Rodrigo
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.forename: Van A
authors.initials: VA
authors.lastname: Doze
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Perez
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D009836:Oligodendroglia / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D011509:Proteoglycans / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D018340:Receptors, Adrenergic, alpha-1 / Q000172:deficiency / Q000378:metabolism*; D013234:Stem Cells; D001616:beta-Galactosidase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000941:Antigens; D049452:Green Fluorescent Proteins; D009638:Norepinephrine; D011509:Proteoglycans; D018340:Receptors, Adrenergic, alpha-1; D001616:beta-Galactosidase; D005680:gamma-Aminobutyric Acid; D000099216:Chondroitin Sulfate Proteoglycan 4; C024884:6-fluoronorepinephrine