RESUMO
Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder. Cell-attached patch clamp recordings confirmed that perisomatic Ih was increased in dorsal CA1 neurons following CUS. Furthermore, when dorsal CA1 Ih was reduced by shRNA-HCN1, the CUS-induced behavioral deficits were prevented. Finally, rats infused in the dorsal CA1 region with thapsigargin, an irreversible inhibitor of the SERCA pump, exhibited anxiogenic-like behaviors and increased Ih, similar to that observed following CUS. Our results suggest that CUS, but not acute stress, leads to an increase in perisomatic Ih in dorsal CA1 neurons and that HCN channels represent a potential target for the treatment of major depressive disorder.
Assuntos
Depressão/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais de Potássio/metabolismo , Estresse Psicológico/fisiopatologia , Potenciais de Ação , Animais , Antidepressivos/metabolismo , Região CA1 Hipocampal/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/fisiologia , Masculino , Neurônios/metabolismo , Técnicas de Patch-Clamp/métodos , Canais de Potássio/genética , Canais de Potássio/fisiologia , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/metabolismo , Tapsigargina/farmacologiaRESUMO
The proteins calbindin-D(28K) and calretinin buffer intracellular calcium and are speculated to be involved in the integration of neuronal signaling. Using Western blot analysis, we compared the levels of calbindin-D(28K) and calretinin in the developing male and female rat hypothalamus on postnatal days (PN) 0, PN2, PN4, PN6, PN8, and PN10. Analysis of variance (ANOVA) of mean calbindin levels indicated a significant effect of sex (p