Fastigial nucleus stimulation ameliorates cognitive impairment via modulating autophagy and inflammasomes activation in a rat model of vascular dementia

Xia, Dongjian; Sui, Rubo; Liu, Min; Zhang, Ling; Zhang, Zhuang

doi:10.1002/jcb.27787

Cited by 13 publications

(6 citation statements)

References 42 publications

(142 reference statements)

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“…VaD is a complex brain disease caused by a decrease in blood supply to the brain and subsequent cognitive dysfunction (26). Studies have shown that VaD is more challenging to treat effectively than AD.…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

et al. 2021

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Background: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM.Methods: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins.Results: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 β) using molecular docking technology. The compounds were found to spontaneously bind to the proteins.Conclusions: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome.In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD

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Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

et al. 2021

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“…Several studies have indicated a protective role of autophagy (Yang C. et al, 2017;Wang F. et al, 2019;Wang N. et al, 2019;Thammisetty et al, 2021). In contrast, multiple studies have reported a detrimental role of autophagy in VCI, which aggregated neuronal death (Jia et al, 2015;Hu et al, 2017;Qin et al, 2018;Su et al, 2018;Xia et al, 2019;Zhang et al, 2019;Tian et al, 2020;Yang et al, 2020). Furthermore, others have indicated that impaired autophagy flux, characterized by elevated autophagosome formation and/or suppressed autophagy degradation, is tightly linked to cell death and cognitive impairment (Xu et al, 2020;Chen et al, 2021).…”

Section: Ric Protects the Neurovascular Unit Neuronsmentioning

confidence: 99%

Therapeutic Potential of Remote Ischemic Conditioning in Vascular Cognitive Impairment

Wang

et al. 2021

Front. Cell. Neurosci.

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Vascular cognitive impairment (VCI) is a heterogeneous disease caused by a variety of cerebrovascular diseases. Patients with VCI often present with slower cognitive processing speed and poor executive function, which affects their independence in daily life, thus increasing social burden. Remote ischemic conditioning (RIC) is a non-invasive and efficient intervention that triggers endogenous protective mechanisms to generate neuroprotection. Over the past decades, evidence from basic and clinical research has shown that RIC is promising for the treatment of VCI. To further our understanding of RIC and improve the management of VCI, we summarize the evidence on the therapeutic potential of RIC in relation to the risk factors and pathobiologies of VCI, including reducing the risk of recurrent stroke, decreasing high blood pressure, improving cerebral blood flow, restoring white matter integrity, protecting the neurovascular unit, attenuating oxidative stress, and inhibiting the inflammatory response.

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“…There are various proposed molecular mechanisms, which include inhibition of mTOR [123], suppression of autophagy-related proteins, stimulation of vascular endothelial growth factor (VEGF) pathway [124], and reduction of proinflammatory cytokines [125].…”

Section: Molecular Mechanism Of Vcimentioning

confidence: 99%

Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits

Hort

Vališ

Kuča

et al. 2019

IJMS

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Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer’s disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.

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Fastigial nucleus stimulation ameliorates cognitive impairment via modulating autophagy and inflammasomes activation in a rat model of vascular dementia

Cited by 13 publications

References 42 publications

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

Exploring the mechanism of Yizhi Tongmai decoction in the treatment of vascular dementia through network pharmacology and molecular docking

Therapeutic Potential of Remote Ischemic Conditioning in Vascular Cognitive Impairment

Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits

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