Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1–42-Induced Mouse Model of Alzheimer’s Disease

Wang, Sulei; Yu, Liu; Yang, Hui; Li, Chaosheng; Zhou, Hui; Xu, Yun; Zhu, Xiaolei

doi:10.1371/journal.pone.0151397

Cited by 43 publications

(38 citation statements)

References 53 publications

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“…Golgi staining was performed using an FD Rapid GolgiStain Kit (FD Neurotechnologies, Columbia, MD, USA) as previously described (Wang et al ., ). Briefly, brain tissues were immersed in impregnation solution consisting equal volumes of Solutions A and B for 2 weeks and then removed to Solution C for 3 days at room temperature in the dark.…”

Section: Methodsmentioning

confidence: 97%

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease

Zhu

Wang

et al. 2017

Aging Cell

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SummaryThe accumulation and deposition of beta‐amyloid (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Histone deacetylases (HDACs) are promising therapeutic targets for the treatment of AD, while the specific HDAC isoforms associated with cognitive improvement are poorly understood. In this study, we investigate the role of HDAC3 in the pathogenesis of AD. Nuclear HDAC3 is significantly increased in the hippocampus of 6‐ and 9‐month‐old APPswe/PS1dE9 (APP/PS1) mice compared with that in age‐matched wild‐type C57BL/6 (B6) mice. Lentivirus ‐mediated inhibition or overexpression of HDAC3 was used in the hippocampus of APP/PS1 mice to investigate the role of HDAC3 in spatial memory, amyloid burden, dendritic spine density, glial activation and tau phosphorylation. Inhibition of HDAC3 in the hippocampus attenuates spatial memory deficits, as indicated in the Morris water maze test, and decreases amyloid plaque load and Aβ levels in the brains of APP/PS1 mice. Dendritic spine density is increased, while microglial activation is alleviated after HDAC3 inhibition in the hippocampus of 9‐month‐old APP/PS1 mice. Furthermore, HDAC3 overexpression in the hippocampus increases Aβ levels, activates microglia, and decreases dendritic spine density in 6‐month‐old APP/PS1 mice. In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD.

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Section: Methodsmentioning

confidence: 97%

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease

Zhu

Wang

et al. 2017

Aging Cell

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“…The dose‐response curve of ORI was not investigated in our study, and thus we can not confirm the optimal dose of ORI for the treatment of sepsis. In our pilot study, sepsis mice were initially treated with ORI at 10 mg/kg which is the most common dose used in available studies [27]. However, the alanine aminotransferase further increased in sepsis mice after ORI treatment.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of oridonin on the sepsis in mice

Zhao¹,

Lv²,

Xu³

et al. 2016

The Kaohsiung J of Med Scie

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This study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)-induced sepsis in mice. Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin-eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.

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“…It has been demonstrated that neurotoxicity and synaptic dysfunction were alleviated with the administration of Ori in Alzheimer's disease mice. 34,50 Synaptic loss is believed to be the basis of cognitive impairment in the MHE. 51 We further confirmed the effect of Ori on the synaptic formation in vivo.…”

Section: Ori Prevents Synaptic Loss In Mhe Ratsmentioning

confidence: 99%

“…[30][31][32] Also, some studies found the impaired behaviour is significantly restored by Ori treatment. 33 Moreover, it has demonstrated that Ori can alleviate neurotoxicity and synaptic dysfunction in AD mice, 34 which means that Ori has the potential application against neurodegenerative disorders. Furthermore, a few studies have investigated that Ori could protect against diabetic nephropathy rats (DN).…”

Section: Introductionmentioning

confidence: 99%

Oridonin prevents insulin resistance–mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy

Wen

Zhuge

Wang

et al. 2019

J Cellular Molecular Medi

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Minimal hepatic encephalopathy (MHE) was characterized for cognitive dysfunction. Insulin resistance (IR) has been identified to be correlated with the pathogenesis of MHE. Oridonin (Ori) is an active terpenoid, which has been reported to rescue synaptic loss and restore insulin sensitivity. In this study, we found that intraperitoneal injection of Ori rescued IR, reduced the autophagosome formation and synaptic loss and improved cognitive dysfunction in MHE rats. Moreover, in insulin‐resistant PC12 cells and N2a cells, we found that Ori blocked IR‐induced synaptic deficits via the down‐regulation of PTEN, the phosphorylation of Akt and the inhibition of autophagy. Taken together, these results suggested that Ori displays therapeutic efficacy towards memory deficits via improvement of IR in MHE and represents a novel bioactive therapeutic agent for treating MHE.

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Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1–42-Induced Mouse Model of Alzheimer’s Disease

Cited by 43 publications

References 53 publications

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease

Protective effects of oridonin on the sepsis in mice

Oridonin prevents insulin resistance–mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy

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