ABSTRACT
Inochinohaha White (IHW) is a Japanese herbal medicine for treating women with anxiety associated with premenstrual syndrome (PMS). In this study, we examined the effects of IHW on anxiety-like behavior in rats undergoing progesterone withdrawal (PWD), a model for PMS. Female rats were injected daily with progesterone for 21 days. Water and ethanol extracts of IHW (WE-IHW and EE-IHW, respectively) were administered orally 15 days after the initiation of progesterone injections. Anxiety-like behavior in an elevated plus maze was evaluated 48 h after the final injection of progesterone. PWD induced anxiety-like behavior, and EE-IHW (300 mg/kg), but not WE-IHW, significantly attenuated this behavior. Administration of the GABA agonists, diazepam or muscimol, significantly attenuated PWD-induced anxiety-like behavior. To investigate the underlying mechanisms of IHW action, we analyzed GABAA receptor expression in the amygdala of these rats. EE-IHW ameliorated the PWD-induced decrease in GABAA receptor ß2-subunit mRNA, although ß2-subunit protein was unchanged. Brain-derived neurotrophic factor (BDNF) has been reported to have anxiolytic effects and enhance GABAergic synaptic transmission. We found that EE-IHW increased BDNF levels in a dose-dependent manner. Our results suggest that EE-IHW attenuates PWD-induced anxiety-like behavior by increasing GABAA receptor-mediated signaling via increases in ß2-subunit and BDNF in the amygdala.
Subject(s)
Anxiety/drug therapy , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Gene Expression/drug effects , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Premenstrual Syndrome/drug therapy , Premenstrual Syndrome/psychology , Receptors, GABA-A/genetics , Receptors, GABA-A/metabolism , Administration, Oral , Amygdala/metabolism , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Injections , Premenstrual Syndrome/genetics , Progesterone/administration & dosage , Rats, WistarABSTRACT
The N-terminal vinculin-homology 1 (VH1) domain of α-catenin facilitates two exclusive forms, a monomeric form directly bound to ß-catenin for linking E-cadherin to F-actin or a homodimer for the inhibition of ß-catenin binding. Competition of these two forms is affected by â¼80 N-terminal residues, whose structure is poorly understood. We have determined the structure of the monomeric free form of the αN-catenin VH1 domain and revealed that the N-terminal residues form α1 and α2 helices to complete formation of the N-terminal four-helix bundle. Dynamic conformational changes of these two helices control formation of the ß-catenin-bound monomer or unbound homodimer.
Subject(s)
alpha Catenin/chemistry , Animals , Chromatography, Gel , Crystallization , Crystallography, X-Ray , Mice , Models, Molecular , Protein ConformationABSTRACT
A dye-linked D-lactate dehydrogenase from the aerobic hyperthermophilic archaeon Aeropyrum pernix was crystallized using the hanging-drop vapour-diffusion method with polyethylene glycol 8000 as the precipitant. The crystals belonged to the monoclinic space group P2(1), with unit-cell parameters a = 63.4, b = 119.4, c = 70.2 Å, ß = 112.0°, and diffracted to 2.0 Å resolution on the BL26B1 beamline at SPring-8. The overall R(merge) was 4.5% and the completeness was 99.8%.
