IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Increased Cardiac Sympathetic Tone Induces Depressive Behavior in Transgenic Mice Overexpressing Cardiac Gs-ALPHA.
Autor/es:
NAHUEL MÉNDEZ DIODATI; CHRISTIAN HÖCHT; JAZMÍN KELLY; STEPHEN VATNER; BRUNO BUCHHOLZ; JULIETA DEL MAURO
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Cardiac specific transgenic (TG) overexpression of Gs protein in mice increases sympathetic drive and cardiac function, which is generally associated with enhanced cardiac activity. The goal of this investigation was to determine if increasing sympathetic tone in this model affected behavior. We subjected TG mice and their wild type (WT) littermates to a novel, open field environment for 2 hours, a forced swimming test, i.e., Porsolt test, for 6 min, a tail suspension test for 6 min, a light/dark box test for 10 min, and a rotarod test. Gs transgenic mice displayed marked hypoactivity, which was characterized by significant reduction in locomotion, jumps, turns and vertical activity in the open field, but no behavioral changes were observed in the home cage. Latency time and swimming time were significantly less in the Porsolt test in TG mice and immobility time in the tail suspension test was higher in the same group. These behavioral changes were reversed by treatment with propranolol. The anxiety test in the light/dark box and motor coordination in the rotarod test were not significantly altered in TG mice. Western blotting confirmed that Gs protein was markedly increased in the heart of TG mice compared to WT, but not in areas of the brain likely involved in the regulation of behavior, such as the amygdala, the olfactory bulb, the hippocampus the midbrain and the striatum. TG mice with cardiac specific overexpression of Gs exhibit enhanced cardiac function, but show blunted behavioral responses to stress, indicative of depression, as confirmed by the Porsolt and tail-suspension test, providing a link between increased sympathetic regulation of the heart and behavior. The novel features of this investigation is the finding of depressive disorders as a result from overexpression of a cardiac protein without primary alterations in the brain, or from enhanced cardiac sympathetic tone.