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

Wei, Binbin; Liu, Mingyan; Chen, Zaixing

doi:10.1038/aps.2017.135

Cited by 31 publications

(19 citation statements)

References 26 publications

(25 reference statements)

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Shen

et al. 2019

Front. Aging Neurosci.

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Olfactory dysfunction is an early event in Alzheimer’s disease (AD). However, the mechanism underlying the AD-related changes in the olfactory bulb (OB) remains unknown. Granule cells (GCs) in the OB regulate the activity of mitral cells (MCs) through reciprocal dendrodendritic synapses, which is crucial for olfactory signal processing and odor discrimination. Nevertheless, the relationships between the morphological and functional changes of dendrodendritic synapses, particularly the local field potentials (LFPs) as a consequence of olfactory disorders in patients with AD have not been investigated. Here, we studied the morphological and functional changes induced by dendrodendritic inhibition in GCs onto MCs in the OB of amyloid precursor protein (APP)/PS1 mice and age-matched control mice during aging, particular, we focused on the effects of olfactory disorder in the dendrodendritic synaptic structures and the LFPs. We found that olfactory disorder was associated with increased amyloid-β (Aβ) deposits in the OB of APP/PS1 mice, and those mice also exhibited abnormal changes in the morphology of GCs and MCs, a decreased density of GC dendritic spines and impairments in the synaptic interface of dendrodendritic synapses between GCs and MCs. In addition, the aberrant enhancements in the γ oscillations and firing rates of MCs in the OB of APP/PS1 mice were recorded by multi-electrode arrays (MEAs). The local application of a GABAAR agonist nearly abolished the aberrant increase in γ oscillations in the external plexiform layer (EPL) at advanced stages of AD, whereas a GABAAR antagonist aggravated the γ oscillations. Based on our findings, we concluded that the altered morphologies of the synaptic structures of GCs, the dysfunction of reciprocal dendrodendritic synapses between MCs and GCs, and the abnormal γ oscillations in the EPL might contribute to olfactory dysfunction in AD.

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Section: Discussionmentioning

confidence: 99%

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

Shen

et al. 2019

Front. Aging Neurosci.

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“…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.…”

Section: Discussionmentioning

confidence: 58%

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

Zhang

Zhao²,

Bai³

et al. 2019

J Biochem & Molecular Tox

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Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti-inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated with schizandrin alone or in combination with lipopolysaccharide (LPS), after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damage as cell viability was repressed and the apoptosis was induced.In the meantime, LPS promoted the release of proinflammatory cytokines including interleukin 1β (IL-1β), IL-8, IL-6, and tumor necrosis factor (TNF-α) while repressing the release of the anti-inflammatory cytokine IL-10. Schizandrin could promote H9c2 cell migration and long-term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS-induced cell loss and inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencing of Smad3 deactivated c-Jun N-terminal kinase (JNK) and nuclear factor κB (NF-κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS-induced injury in the H9c2 cells and promoted the recovery of myocardial tissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF-κB pathways. K E Y W O R D S H9c2 cell, lipopolysaccharide, myocarditis, schizandrin, Smad3

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Schisandrin, an active component extracted from Schisandra chinensis (Turcz.) Baill has been reported to alleviate the cognitive impairment in neurodegenerative disorder like Alzheimer's disease (AD). However, the mechanism by which schisandrin regulates the cognitive decline is still unclear. In our study, intracerebroventricular injection of streptozotocin (STZ) was employed to establish AD model in male Wistar rats, and indicated dose of schisandrin was further administered. The Morris water maze test was performed to evaluate the ability of learning and memory in rats with schisandrin treatment. The results indicated that schisandrin improved the capacity of cognition in STZ-induced rats. The contents of pro-inflammatory cytokines in brain tissue were determined by ELISA, and the expressions of these cytokines were assessed by western-blot and immunohistochemistry. The results showed that treatment of schisandrin significantly reduced the production of inflammation mediators including tumor necrosis factor-α, interleukin-1β and interleukin-6. Further study suggested a remarkable decrease in the expressions of ER stress maker proteins like C/EBP-homologous protein, glucose-regulated protein 78 and cleaved caspase-12 in the presence of schisandrin, meanwhile the up-regulation of sirtuin 1 (SIRT1) was also observed in the same group. Additionally, the results of western-blot and EMSA demonstrated that schisandrin inhibited NF-κB signaling in the brain of STZ-induced rats. In conclusion, schisandrin ameliorated STZ-induced cognitive dysfunction, ER stress and neuroinflammation which may be associated with up-regulation of sirtuin 1 (SIRT1). Our study provides novel mechanisms for the neuroprotective effect of 3 schisandrin in AD treatment.

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

Cited by 31 publications

References 26 publications

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

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

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

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

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