Abstract
Stress can induce learning and memory impairment; corticosterone is often used to study the effects and mechanisms of stress in animal models. Long-term potentiation (LTP) has been widely used for tackling the mechanisms of memory. Liuwei Dihuang decoction-active fraction combination (LW-AFC) can improve stress-induced LTP and cognition impairment; stachyose is an oligosaccharide in LW-AFC. The effects and mechanisms of stachyose on stress are unknown. In this study, stachyose showed protective effects against LTP impairment by corticosterone in vivo only via intragastric administration for 7 consecutive days, but there was little effect even after direct intracerebroventricular injection; the protective effect of stachyose could be canceled by non-absorbable antibiotics (ATB) which disturbed gut flora. 16S rRNA sequencing, alpha diversity, and principal coordinate analysis (PCoA) revealed that the gut flora in corticosterone-treated mice was disturbed and stachyose could improve corticosterone-induced gut flora disturbance. Bacteroidetes were decreased and Deferribacteres were increased significantly in corticosterone-treated mice, and stachyose restored Bacteroidetes and Deferribacteres to the normal level. D-serine, a coactivator of NMDA receptors, plays an important role in synaptic plasticity and cognition. Here, corticosterone had little effect on the content of D-serine and L-serine (the precursor of D-serine), but it reduced the D-serine release-related proteins, Na+-independent alanine–serine–cysteine transporter-1 (ASC-1), and vesicle-associated membrane protein 2 (VAMP2) significantly in hippocampus; stachyose significantly increased ASC-1 and VAMP2 in corticosterone-treated mice, and ATB blocked stachyose’s effects on ASC-1 and VAMP2. NMDA receptors co-agonists L-serine, D-serine, and glycine significantly improved LTP impairment by corticosterone. These results indicated that stachyose might indirectly increase D-serine release through the gut–brain axis to improve LTP impairment by corticosterone in the hippocampus in vivo.
Highlights
Stress can activate the hypothalamic–pituitary–adrenal (HPA) axis and elevate glucocorticoids in the body
For further understanding the active ingredients and mechanisms of oligosaccharide fraction of LW-active fraction combination (LW-AFC) (CA-30), in this study, we focused on the effects of stachyose, on Long-term potentiation (LTP) impairment by corticosterone, gut flora, and the D-serine pathway
According to our previous study, 0.8 g/kg to 3.2 g/kg of LW-AFC could protect LTP impairment against corticosterone (Huang et al, 2019); LW-AFC contains 64.6% oligosaccharide fraction, that is, the theoretical effective dosage of oligosaccharide fraction is ranged from 520 mg/kg to 2080 mg/kg
Summary
Stress can activate the hypothalamic–pituitary–adrenal (HPA) axis and elevate glucocorticoids in the body (cortisol in humans and corticosterone in rodents) (de Kloet et al, 2005). Glucocorticoid receptors are abundant in the hippocampus and play an important role in stress-induced cognition alteration (De Kloet et al, 1998; Kim and Yoon, 1998; Rogalska, 2010). As a main form of synaptic plasticity, long-term potentiation (LTP) is believed to represent the cellular correlates of learning and memory (Lüscher and Malenka, 2012), and stress or corticosterone-induced cognitive impairment are closely related to LTP deficiency (Pavlides et al, 1993; Kim et al, 2006; Howland and Wang, 2008; Aisa et al, 2009). Modulating gut flora contributes to the neuroprotective effects of LW-AFC and CA-30 (Huang et al, 2019; Wang et al, 2019; Cheng et al, 2020a). For further understanding the active ingredients and mechanisms of CA-30, in this study, we focused on the effects of stachyose, on LTP impairment by corticosterone, gut flora, and the D-serine pathway
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