Schisandrin ameliorates cognitive impairment and attenuates Aβ deposition in APP/PS1 transgenic mice: involvement of adjusting neurotransmitters and their metabolite changes in the brain

Abstract

Neurotransmitters (NTs) in the brain are involved in neurodegenerative diseases, such as Alzheimer's disease (AD). Schisandrin is a major ingredient of Schisandra chinensis (Turcz.) Baill and has been used for the treatment of AD. In this study we examined the therapeutic effects of schisandrin in APP/PS1 transgenic mice, and correlated the beneficial effects on cognitive impairment with the adjustments in NTs and their metabolites in the mouse brains. APP/PS1 mice were treated with schisandrin (2 mg·kg·d, ip) for 2 weeks. In Morris Water Maze test; untreated APP/PS1 mice displayed significant cognitive impairment compared with normal mice; schisandrin administration ameliorated the cognitive impairment and significantly decreased Aβ deposition in the hippocampus. In order to assess the effects of schisandrin on NTs and their metabolites, we developed a rapid and sensitive UPLC-MS/MS method for simultaneous determination of serotonin, 5-hydroxyindole acetic acid, dopamine, norepinephrine, γ-aminobutyric acid, glutamic acid, homovanillic acid, 3,4-dihydroxyphenylacetic acid and acetylcholine in mouse brains. This method conformed to methodology validation requirements. We found that there were statistically significant differences in these NTs and their metabolites between untreated APP/PS1 mice and normal mice, whereas schisandrin administration restored the abnormal NTs and their metabolites levels. These results suggest that schisandrin could alter the levels of these NTs and their metabolites in the brain, thus ameliorating learning and memory impairments in APP/PS1 mice.

Impairment of Dendrodendritic Inhibition in the Olfactory Bulb of APP/PS1 Mice

“…In addition, it has been hypothesized that Aβ deposits in the olfactory system promote AD pathology in rodents (Wesson et al, 2010, 2011). In vivo , excessive Aβ depositions within the hippocampus lead to learning and memory deficits (Kim et al, 2013; Birnbaum et al, 2015; Lei et al, 2016; Wei et al, 2018). Similarly, Aβ depositions in the OB affected olfactory-related behavioral performances in APP/PS1 mice.…”

Schizandrin protects H9c2 cells against lipopolysaccharide‐induced injury by downregulating Smad3

“…We additionally found that pretreatment with schizandrin could prevent H9c2 cells against an LPS‐induced inflammatory response. Actually, schizandrin has been involved in recent in vivo and in vitro pharmacological studies suggesting a protective effect in various pathological models including APP/PS1 transgenic mice, chronic unpredictable mild stress in mice, ovariectomized (OVX) and non‐OVX rats, TGF‐β1‐stimulated AML12 cells, and cisplatin‐stimulated HK‐2 cells . Our findings for the first time demonstrated that schizandrin could prevent LPS‐induced cell damage by influencing the release of inflammatory cytokines.…”

Schisandrin ameliorates cognitive deficits, endoplasmic reticulum stress and neuroinflammation in streptozotocin (STZ)-induced Alzheimer’s disease rats

“…Preclinical studies have found the memory and learning deficits along with the observation of cerebral atrophy, amyloid plaques, and neurofibrillary tangles in STZ-treated rats [ 13 ]. Schisandrin has been suggested the potential to exert the neuroprotective effect on Alzheimer’s disease [ 27 ]. The Morris water maze test was performed in our study after the treatment of schisandrin.…”