Korean Red Ginseng reduces chronic social defeat stress-induced mood disorders via N-methyl-D-aspartate receptor modulation in mice

Abstract

Background A chronic social defeat stress (CSDS) model has been proposed as relevant to stress-induced behavioral change in humans. In this study, we examined the effect of Korean Red Ginseng (KRG) on CSDS-induced mood disorders and protein expression in an animal model. Methods To evaluate the effect of KRG on social defeat stress, test mice were exposed in the resident aggressor's home cage compartment for 14 days beginning 1 h after KRG treatment (10, 20, and 40 mg/kg, per oral (p.o.)). After the exposure, behavioral tests to measure anxiety, social interaction, and depression-like behavior were performed. To investigate the underlying mechanism, N-methyl-D-aspartate receptor expression levels in CSDS-induced mice were evaluated using Western blot analysis. Results CSDS induced anxiety-like behaviors by decreasing central activity in the open-field test and open-arm approach in the elevated plus maze test and led to social avoidance behavior in the social interaction test. CSDS mice showed upregulated NR1, NR2A, and NR2B expression in the hippocampus. KRG 20 and 40 mg/kg ameliorated anxiety-like activities and KRG 20 mg/kg alleviated social avoidance by decreasing time in the corner zone. KRG treatment recovered CSDS-induced NR1, NR2A, and NR2B protein levels in the hippocampus. Conclusion These results indicate that KRG has a therapeutic effect on CSDS-induced mood disorder by alleviating N-methyl-D-aspartate receptor overexpression in the hippocampus.

Effect of caffeine on hippocampal memory and levels of gene expression in social isolation stress

“…Our study shows NR2A gene expression increased in the SI and SICf groups compared with the C and Cf groups. In other studies, exposure to SI for 8 weeks, starting with PND21 in rats, and the chronic stress of social defeat in mice have been shown to upregulate both NR2A and NR2B in the hippocampus (Lee et al, 2021; Zhao et al, 2009). Increased postsynaptic receptors on the postsynaptic membrane may indicate cognitive dysfunction associated with glutamate neurotoxicity (Cao et al, 2018).…”

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“…Western blot was carried out as previously reported in [ 18 ]. In this paper, the following primary antibodies were used; anti-β-actin, anti-adenylyl cyclase 1 (AC1), anti-Ca 2 ⁺/calmodulin-dependent protein kinase II (CaMKⅡ), anti-phosphorylated CaMKII (pCaMKⅡ), anti-dopamine transporter (DAT), anti-pDAT, anti-D1DR, anti-D2DR, anti-extracellular signal-regulated kinase (ERK), anti-pERK, anti-NR1, anti-NR2A, anti-NR2B, anti-protein kinase A (PKA), and anti-postsynaptic density protein 95 (PSD-95).…”

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“…This test was performed with minor modifications of previously reported experimental designs (Lee et al, 2019) to evaluate the social withdrawal as an indicator of a negative symptom in schizophrenia (Onaolapo et al, 2017). A customised wire cage (11 × 11 × 25 cm) was located in the middle of one wall of the open field box (30 × 30 × 30 cm).…”

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