Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aβ1–42-Treated Rats

Song, Xiao-Yu; Liu, Bo; Cui, Lingyu; Zhou, Biao; Liu, Lu; Liu, Weiwei; Yao, Guo-Dong; Xia, Mingyu; Hayashi, Toshihiko; Hattori, Shunji; Ushiki-Kaku, Yuko; Tashiro, Shin‐ichi; Ikejima, Takashi

doi:10.1007/s11064-018-2481-3

Cited by 23 publications

(9 citation statements)

References 38 publications

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“…High levels of estrogen in females may provide protection against inflammation and disruptions in neurotransmission that adversely impact cognition. It has been well established that estrogen and its receptors play multiple key neuroprotective roles in preventing a variety of neurodegenerative disorders, including cognitive deficits and mood disorders (Behl and Manthey, 2000;Norbury et al, 2003;Pratap et al, 2016;Song et al, 2018). Increased estrogen has antioxidant and anti-inflammatory properties (Lu et al, 2019) and may also promote axonal and dendritic growth, thereby protecting against the radiation-induced reductions in dendritic morphology and spine density known to occur in male mice subjected to various types of cosmic radiation exposure (Parihar et al, 2015a(Parihar et al, , 2016.…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Cognitive Deficits Following Space Radiation Exposure

Parihar

Angulo

Allen

et al. 2020

Front. Behav. Neurosci.

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The radiation fields in space define tangible risks to the health of astronauts, and significant work in rodent models has clearly shown a variety of exposure paradigms to compromise central nervous system (CNS) functionality. Despite our current knowledge, sex differences regarding the risks of space radiation exposure on cognitive function remain poorly understood, which is potentially problematic given that 30% of astronauts are women. While work from us and others have demonstrated pronounced cognitive decrements in male mice exposed to charged particle irradiation, here we show that female mice exhibit significant resistance to adverse neurocognitive effects of space radiation. The present findings indicate that male mice exposed to low doses (≤30 cGy) of energetic (400 MeV/n) helium ions (4 He) show significantly higher levels of neuroinflammation and more extensive cognitive deficits than females. Twelve weeks following 4 He ion exposure, irradiated male mice demonstrated significant deficits in object and place recognition memory accompanied by activation of microglia, marked upregulation of hippocampal Toll-like receptor 4 (TLR4), and increased expression of the pro-inflammatory marker high mobility group box 1 protein (HMGB1). Additionally, we determined that exposure to 4 He ions caused a significant decline in the number of dendritic branch points and total dendritic length along with the hippocampus neurons in female mice. Interestingly, only male mice showed a significant decline of dendritic spine density following irradiation. These data indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.

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Section: Discussionmentioning

confidence: 99%

Sex-Specific Cognitive Deficits Following Space Radiation Exposure

Parihar

Angulo

Allen

et al. 2020

Front. Behav. Neurosci.

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“…The accumulation of misfolded proteins in the lumen of the endoplasmic reticulum results in dysfunction of the endoplasmic reticulum, inducing endoplasmic reticulum stress (ERS) [6]. A large number of studies have shown that ERS is closely related to the occurrence of AD [7–9].…”

Section: Introductionmentioning

confidence: 99%

Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

Liu

Yang

2019

BioMed Research International

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Aim. To investigate the effect of crocin on the learning and memory acquisition of AD rats and its underlying mechanisms. Methods. A total of 48 healthy male SD rats were randomly divided into control group, AD model group, resveratrol group, and crocin group, with 12 rats per group. AD model was established by injecting Aβ25–35 to the lateral ventricle of rats, and thereafter the rats were administrated with resveratrol (40 mg/kg), crocin (40 mg/kg), or PBS daily for 14 days. Y-maze test and sucrose preference test were used to detect the learning and memory acquisition of rats. Neuronal apoptosis was detected by TUNEL staining and Western blot for apoptosis-related proteins Bax, Bcl-2, and Caspase-3. Immunofluorescence staining and Western blot tests were used to detect the expression of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in hippocampal CA1 region (Hippo) and prefrontal cortical neurons (PFC). Results. The learning and memory abilities of AD rats were significantly decreased, which was significantly rescued by resveratrol and crocin. The apoptotic cell number of Hippo and PFC neurons in AD model group was significantly higher than that in control group (P<0.01), while resveratrol and crocin significantly decreased the apoptotic cell number in AD group (P<0.01). Compared with the control group, the expression of Bcl2 in PFC and hippo of AD model group was significantly decreased (P<0.01), while those of Bax, Caspase3, GRP78, and CHOP were significantly increased (P<0.01). Resveratrol and crocin could significantly reverse the expression of these proteins in AD rats (P<0.05). Conclusion. Crocin can improve the learning and memory ability of AD rats possibly by reducing endoplasmic reticulum stress and neuronal apoptosis.

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“…ERS serves a vital role in the earliest stages of AD pathogenesis (6). Recent studies have demonstrated that the toxic peptide, Aβ, induces ERS and then activates the unfolded protein response (8,13). It has been reported that ERS is involved in the cleavage of Aβ protein precursor, thus promoting the production of Aβ and facilitating the development of AD (14–16).…”

Section: Discussionmentioning

confidence: 99%

“…These explanations include the endoplasmic reticulum stress (ERS) hypothesis, the genetic factor hypothesis, the cholinergic hypothesis and the lack of nerve growth factor hypothesis (2,3) Among these hypotheses, the ERS hypothesis appears to be the most probable as ERS is induced by oxidative stress; ERS occurs in the earliest stages of AD pathogenesis (4). Numerous studies have attempted to ameliorate ERS as a therapy for AD (5–8); however, the specific molecular mechanisms that lead to ERS during the pathological progression of AD remain unknown. In the present study, these mechanisms and potential targeting approaches were investigated in an in vitro model of AD (6).…”

Section: Introductionmentioning

confidence: 99%

Astragaloside IV ameliorates endoplasmic reticulum stress‑induced apoptosis of Aβ25‑35‑treated PC12 cells by inhibiting the p38�MAPK signaling pathway

2019

Mol Med Report

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Endoplasmic reticulum stress (ERS) serves a vital role in the pathological development of Alzheimer's disease (AD). ERS can promote programmed cell death (apoptosis) during AD; however, the specific molecular mechanisms that lead to ERS remain unclear. It is very important that a drug for the treatment of AD is identified. Our previous studies indicated that astragaloside IV (AST IV) has anti-inflammatory effects and helps cells resist oxidative stress. In the present study, western blotting and reverse transcription semi-quantitative polymerase chain reaction were used to detect protein and mRNA expression levels, flow cytometry was used to measure intracellular reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) and malondialdehyde (MDA) activity was detected using commercially available kits. The results demonstrated that SOD activity was decreased, and MDA content, ROS levels, and the expression levels of p38 mitogen-activated protein kinase (MAPK) and ERS-associated proteins, including binding immunoglobulin protein/glucose-regulated protein and growth arrest- and DNA damage -inducible gene 153/C/EBP homologous protein, were increased in amyloid β (Aβ) 25-35 -treated PC12 cells. Furthermore, to investigate the role of p38 MAPK and the effects of AST IV in an in vitro model of AD, SB203580, a p38 MAPK signaling pathway inhibitor, and AST IV were administered to Aβ 25-35 -treated PC12 cells. The results revealed that AST IV protected the cells against AD. This effect may be caused by decreases in ROS levels, which may inhibit the p38 MAPK signaling pathway and thereby suppress ERS in Aβ 25-35 -treated PC12 cells.

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Estrogen Receptors Are Involved in the Neuroprotective Effect of Silibinin in Aβ1–42-Treated Rats

Cited by 23 publications

References 38 publications

Sex-Specific Cognitive Deficits Following Space Radiation Exposure

Sex-Specific Cognitive Deficits Following Space Radiation Exposure

Crocin Improves Cognitive Behavior in Rats with Alzheimer's Disease by Regulating Endoplasmic Reticulum Stress and Apoptosis

Astragaloside IV ameliorates endoplasmic reticulum stress‑induced apoptosis of Aβ25‑35‑treated PC12 cells by inhibiting the p38�MAPK signaling pathway

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