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Alpha‐1A adrenergic receptors regulate neurogenesis and cognitive function
Author(s) -
Boese Sarah Jane,
Schlosser Danielle D,
Knudson Chris A,
Carr Patrick A,
Perez Dianne M,
Doze Van A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.812.4
Subject(s) - morris water navigation task , neurogenesis , hippocampal formation , knockout mouse , hippocampus , water maze , genetically modified mouse , receptor , neuroscience , agonist , stimulation , transgene , conditional gene knockout , chemistry , endocrinology , medicine , biology , biochemistry , phenotype , gene
A major target of the adrenergic system is the hippocampus, a region that is critical for learning and memory. Recent studies suggest alpha‐1A adrenergic receptors (α 1A ‐ARs) may regulate neurogenesis and neuronal differentiation. Our understanding of the function of α 1A ‐ARs is limited due to a lack of specific ligands and antibodies. To address this, transgenic mice were generated which over‐express the α 1A ‐AR with enhanced green fluorescent protein (EGFP) or constitutively active mutant (CAM) α 1A ‐AR. Knockout (KO) α 1A mice were also generated. Immunohistochemistry showed that CAM α 1A ‐AR mice had increased BrdU incorporation compared to normal and KO α 1A ‐AR mice. Increased numbers of hippocampal interneurons in CAM α 1A mice compared to normal mice were also observed. Increased interneurons may affect learning and memory. Normal, CAM α 1A , and KO α 1A mice were tested on a multi‐component T‐maze and the Morris water maze. CAM α 1A mice displayed increased cognitive ability in the T‐maze and the Morris water maze compared to normal mice. In both models, KO α 1A ‐AR mice displayed the worst cognitive ability. Treating normal mice with the selective α 1A ‐AR agonist cirazoline also showed enhanced learning and memory processes. Stimulation of α 1A ‐ARs may offer a new therapeutic strategy for increasing cognitive function and treating neurodegenerative diseases. Supported by NIH, NIH COBRE, NSF ND EPSCoR, NSF CAREER.