SK2 potassium channel overexpression in basolateral amygdala reduces anxiety, stress-induced corticosterone secretion and dendritic arborization

• Published in: Molecular psychiatry Vol. 14; no. 9; pp. 847 - 855
• Main Authors: Mitra, R, Ferguson, D, Sapolsky, R M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2009; Nature Publishing Group
• Subjects: Amygdala; Amygdala (Brain); Amygdala - metabolism; Amygdala - pathology; Analysis of Variance; Animal memory; Animals; Anxiety; Anxiety - etiology; Anxiety - pathology; Anxiety - physiopathology; Anxiety - therapy; Behavior, Animal; Behavioral Sciences; Biological Psychology; Control; Corticosterone; Corticosterone - blood; Dendrites - pathology; Dendritic branching; Disease Models, Animal; Gene therapy; Genetic aspects; Genetic Therapy - methods; Genetic Vectors - physiology; Germinal Center Kinases; Glucocorticoids; Health aspects; Herpes simplex; Locomotion - genetics; Male; Maze Learning - physiology; Medicine; Medicine & Public Health; Mental disorders; Neurons; Neurons - pathology; Neurosciences; original-article; Pharmacotherapy; Physiological aspects; Potassium; Potassium channels; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Psychiatry; Rats; Rats, Wistar; Risk factors; Secretion; Simplexvirus - genetics; Simplexvirus - physiology; Stress, Psychological; Therapeutic targets; United States; herpes simplex virus; gene therapy; stress hormone; rats; brain; hypertrophy
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2009.9

The basolateral amygdala is critical for generation of anxiety. In addition, exposure to both stress and glucocorticoids induces anxiety. Demonstrated ability of the amygdala to change in response to stress and glucocorticoids could thus be important therapeutic target for anxiety management. Several studies have reported a relationship between anxiety and dendritic arborization of the amygdaloid neurons. In this study we employed a gene therapeutic approach to reduce anxiety and dendritic arborization of the amygdala neurons. Specifically, we overexpressed SK2 potassium channel in the basolateral amygdala using a herpes simplex viral system. Our choice of therapeutic cargo was guided by the indications that activation of the amygdala might underlie anxiety and that SK2 could reduce neuronal activation by exerting inhibitory influence on action potentials. We report that SK2 overexpression reduced anxiety and stress-induced corticosterone secretion at a systemic level. SK2 overexpression also reduced dendritic arborization of the amygdala neurons. Hence, SK2 is a potential gene therapy candidate molecule that can be used against stress-related neuropsychiatric disorders such as anxiety.