Abstract
BackgroundSo-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.
Highlights
-ochim-tang-gamibang (SOCG) is a decoction formula which has been used to improve mental activity in traditional Korean medicine
To examine whether SOCG treatment in chronic restraint stress (CRS) mice alters the expression of stress-related genes in the hippocampus, expressions of mRNAs encoding Serotonin 1A receptor (5-HT1AR), 5HT1BR, Corticotropin-releasing hormone receptor type 1 receptor (CRF1) and 2, and glucocorticoid receptor were analyzed by Reverse transcription-polymerase chain reaction (RT-PCR). 5-HT1AR mRNA was expressed in control animals and was significantly decreased after CRS (Fig. 1a). Serotonin 1B receptors (5-HT1BR) mRNA levels were decreased by CRS and elevated by SOCG treatment
CRF1 and glucocorticoid receptor (GR) mRNA levels remained constant by CRS and SOCG (Fig. 1c,d)
Summary
-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). Depression is a mental illness that causes a serious disability of the quality of life and affects about 20% of the population worldwide. Recent advances in brain imaging techniques have identified the anterior cingulate cortex, hippocampus, and amygdala as susceptible brain areas to depressive illness in human [1,2,3]. Studies using experimental animals indicate that the intense, chronic stress activates the hypothalamus-pituitary-adrenal gland (HPA) axis, and elevated glucocorticoid hormone levels cause neuronal atrophy in several brain areas. Major inputs to hippocampus are given from the entorhinal cortex
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