Ablation of Neurogenesis in α1A‐Adrenergic Receptor Activated Mice

Abstract

It is unclear what role α1A‐adrenergic receptors (ARs) have on neurogenesis, cognition and mood. The goal of this study is to examine how the α1A‐ARs relationship to neurogenesis influences cognition and mood. Mice over‐expressing the α1A‐AR showed increased cognition and neurogenesis over normal mice. We hypothesize activation of the α1A‐AR alone is not responsible for improvements in cognition and mood, but it is the receptor‐stimulated neurogenesis. To test this hypothesis, mice are treated with selective α1A‐AR agonist, cirazoline (CRZ). A cannula and osmotic pump is surgically inserted into mice with either artificial cerebral spinal fluid or anti‐mitotic agent cytosine arabinoside (AraC). Mice undergo behavioral testing (Morris water maze, novel object recognition, forced swim, tail suspension, and open field), are sacrificed, brains fixed, sectioned and stained with cell markers for immature and dividing neurons. Stereology was used to estimate cell populations. Preliminary results show AraC mice are significantly slower in solving the Morris Water Maze than AraC‐CRZ mice. The results of this study may lead to development of therapeutic strategies for neurodegenerative diseases. Support: NSF Graduate Research Fellowship Program Grant, NSF Grant EPS‐0447679, NSF CAREER Grant 0347259, NIH Grant 5P20RR017699.