Antidepressant effect of BE360, a new selective estrogen receptor modulator, activated via CREB/BDNF, Bcl-2 signaling pathways in ovariectomized mice.
We have previously reported that the carborane compound BE360, a novel selective estrogen receptor modulator, has a therapeutic potential against dementia. This study aimed to explore the effects and underlying mechanisms of BE360 on depression-like behaviors in ovariectomized (OVX) mice subjected to subchronic stress, which are postmenopausal depression models. BE360 was subcutaneously administrated using a mini-osmotic pump, for 2 weeks. Depression-like behaviors were evaluated using the forced swimming test. Neurogenesis in the hippocampal dentate gyrus (DG) was measured by analyzing cells expressing doublecortin (DCX) following 5-bromo-2'-deoxyuridine (BrdU) uptake. The levels of phosphorylated cyclic-AMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and Bcl-2 were measured using immunohistochemistry or immunoblotting. Depression-like behaviors in OVX + Stress-exposed mice improved after chronic treatment with BE360. BE360 treatment in OVX + Stress-exposed mice increased p-CREB, BDNF, and Bcl-2 expressions in the hippocampus. Immunohistochemistry showed that the number of BrdU/DCX double-positive cells in the DG of the hippocampus, which decreased significantly in OVX + Stress-exposed mice, increased after subchronic treatment with BE360. The present study demonstrates that BE360 exerts antidepressant effects via hippocampal neurogenesis, potentially activated through CREB/BDNF, Bcl-2 signaling pathways. These results indicate that BE360 may have therapeutic potential against postmenopausal depression.
['Sakuma|Wakana|W|', 'Nakagawasai|Osamu|O|', 'Nemoto|Wataru|W|', 'Odaira|Takayo|T|', 'Ogawa|Takumi|T|', 'Ohta|Kiminori|K|', 'Endo|Yasuyuki|Y|', 'Tan-No|Koichi|K|']
D000818:Animals D000928:Antidepressive Agents D001522:Behavior, Animal D001896:Boron Compounds D019208:Brain-Derived Neurotrophic Factor D017362:Cyclic AMP Response Element-Binding Protein D003863:Depression D000089662:Doublecortin Protein D005260:Female D006624:Hippocampus D051379:Mice D010052:Ovariectomy D019253:Proto-Oncogene Proteins c-bcl-2 D020845:Selective Estrogen Receptor Modulators D015398:Signal Transduction
Selective estrogen receptor modulator Carborane compound Depression Neurogenesis Menopause Ovariectomy