Modulation of hippocampal neuronal activity by So-ochim-tang-gamibang in mice subjected to chronic restraint stress

Abstract

Background So-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine. The present study was performed to evaluate whether the treatment of SOCG was involved in activating hippocampal neurons in mice which were subjected to chronic restraint stress (CRS).MethodsMice were subjected to CRS for 2 weeks to induce depressive-like behaviors. SOCG was orally administered for the same period. mRNA expression in the hippocampus was analyzed by RT-PCR. Levels of serotonin receptor 5-HT1AR in the hippocampus were determined by western blotting and by immunofluorescence staining in coronal brain sections. Cultured neurons were prepared from the dorsal root ganglia (DRG) in mice to examine the effects of CRS and SOCG treatment on neurite outgrowth. Depressive-like behaviors of experimental animals were measured by open field test (OFT) and forced swimming test (FST).ResultsmRNA levels of serotonin 1A and 1B receptors (5-HT1AR and 5-HT1BR) were decreased in the hippocampus of CRS animals and increased by SOCG treatment. Signals of 5-HT1AR protein in CA3 pyramidal cells were decreased by CRS but elevated back to levels in control animals after SOCG treatment. Phospho-Erk1/2 protein in CA3 cells showed similar pattern of changes as in 5-HT1AR, suggesting coordinated regulation after SOCG treatment in CRS animals. Axonal growth-associated protein GAP-43 levels were also decreased by CRS and then increased by SOCG treatment. In vivo administration of SOCG improved neurite outgrowth of primary DRG neurons from CRS animals and also increased 5-HT1AR protein signals. Behavioral tests of open field and forced swimming showed that immobility time periods were significantly decreased by SOCG treatment.ConclusionsOur data suggest that SOCG treatment may increase synaptic responsiveness to serotonergic neuronal inputs by upregulating 5-HT1AR in the hippocampal neurons.

Hippocampal activation of 5‐HT1B receptors and BDNF production by vagus nerve stimulation in rats under chronic restraint stress

“…Chronic VNS was applied to animals that had undergone CRS. CRS was given to rats as described previously (Shin et al., ). Briefly, rats were placed in a well‐ventilated cylindrical shape of Plexiglas container for 6 hr (9:00 a.m.–15:00 p.m.) each day for 14 days.…”

“…Forced swimming test was performed as previously described (Bogdanova, Kanekar, D'Anci, & Renshaw, ; Shin et al., ). Each rat was placed in a transparent cylindrical chamber (height 50 cm, diameter 25 cm) filled with water at 27℃ (depth 40 cm).…”

“…For open field test (OFT), rats in three experimental groups (CTL, CRS + Sham, CRS + VNS) were prepared as described above and were subjected to the test as described previously (Cheng et al., ; Shin et al., ). Briefly, animals were adjusted by placing in a test room for 1 hr and placed into a square chamber (70 × 70 × 40 cm 3 ).…”

Efficacy and safety of oral SOCG in treatment of major depressive disorder

“…SOCG has been shown to have reasonable antidepressant activity in animal behavior studies compared to different antidepressant treatments. It has also been patented as a composition for treating depressive disorder [13,14] (Registered patent of Republic of Korea 10-1910013). However, clinical effects in humans through well-designed trials have not been assessed.…”