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[[alpha].sub.1a] adrenergic receptors enhance neurogenesis, learning & memory, and alleviate depression and anxiety in adult mice.

Neurogenesis, the production of new cells, continues in the brain throughout adulthood. The most active areas of adult neurogenesis are the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyms. A major target of the noradrenergic system is the hippocampus, a region that is critical for learning and memory. Recent studies suggest the noradrenergic alpha-lA adrenergic receptors ([[alpha].sub.1a]-ARs) may regulate neurogenesis. This regulation may have additional behavioral effects on cognition, learning, memory, anxiety and depression. However, our understanding of the function of [[alpha].sub.1a]ARS is limited due to a lack &specific ligands and antibodies. To address this, transgenic mice were generated which over-express either the [[alpha].sub.1a]AR with enhanced green fluorescent protein (EGFP) or a constitutively active mutant (CAM) [[alpha].sub.1a]AR. Knockout (KO) [[alpha].sub.1a]AR mice were also generated. Immunohistochemistry showed that CAM [[alpha].sub.1a]AR mice had increased BrdU incorporation compared to normal and KO [[alpha].sub.1a]AR mice in both the SVZ and SGZ. Treating normal mice with the selective [[alpha].sub.1a]AR agonist also increased adult neurogenesis. The CAM[[alpha].sub.1a]AR mice showed improved performance in behavioral tests for depression and anxiety (Tail Suspension Test, Marble Burying Test and Light Dark Exploration), as well as tests for cognition, learning and memory (Barnes Maze). These results suggest that stimulation of [[alpha].sub.1a]ARs may offer a new strategy for alleviating depression and anxiety, and treating neurodegenerative diseases.

Brianna L. Goldenstein [1]*, Mariaha J. Lyons [1], Katie M. Collette [1], Sarah Wood [1], Brian W. Nelson [1], Ruby Fagerlie [1], James Haselton [1], Dianne M. Perez [2], Van A. Doze [1]

[1] Department of Pharmacology, Physiology & Therapeutics, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND 58202

[2] Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, OH
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Title Annotation:Graduate Communication in the A. Roger Denison competition
Author:Goldenstein, Brianna L.; Lyons, Mariaha J.; Collette, Katie M.; Wood, Sarah; Nelson, Brian W.; Fager
Publication:Proceedings of the North Dakota Academy of Science
Date:Apr 1, 2010
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