SK2 potassium channel overexpression in basolateral amygdala reduces anxiety, stress-induced corticosterone secretion and dendritic arborization.
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.
Mitra
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Department of Biology, Stanford University, Stanford, CA 94305, USA. rupshi@stanford.edu
Ferguson
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Sapolsky
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RM
D000679:Amygdala / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D001522:Behavior, Animal; D003345:Corticosterone / Q000097:blood*; D003712:Dendrites / Q000473:pathology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000502:physiology; D000081410:Germinal Center Kinases; D008124:Locomotion / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology; D013315:Stress, Psychological; D000099317:Hippo Kinases
D003345:Corticosterone; D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases; C481222:Slk protein, rat; D000099317:Hippo Kinases