C‐type lectin‐like receptor 2 and zonulin are associated with mild cognitive impairment and Alzheimer's disease

Wang, Xin; Liu, Guo Jun; Gao, Qiang; Li, Na; Wang, Rui‐tao

doi:10.1111/ane.13196

Cited by 32 publications

(23 citation statements)

References 34 publications

(51 reference statements)

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“…Additionally, these antioxidant genes are associated with immune responses, especially inflammation. Most of these genes (S100a8, S100a9, Prdx2, Hp, and Mpst) were also associated with AD in earlier studies [ 74 , 75 , 76 , 77 , 78 , 79 ]. Furthermore, the upregulation of 28 genes in the immune system database and 33 in the innate gene DBs could have directly contributed to the acquired and innate immunity in the ADM mice+C3G group, respectively.…”

Section: Discussionmentioning

confidence: 75%

Comparative Transcriptome Analysis of the Expression of Antioxidant and Immunity Genes in the Spleen of a Cyanidin 3-O-Glucoside-Treated Alzheimer’s Mouse Model

2021

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Cyanidin 3-O-glucoside (C3G) is a well-known antioxidant found as a dietary anthocyanin in different fruits and vegetables. It has protective and therapeutic effects on various diseases. It can reduce neuronal death from amyloid-beta (Aβ)-induced toxicity and promote the inhibition of Aβ fibrillization. Antioxidant and immune modulation might play a critical role in the properties of C3G against Alzheimer’s disease (AD) and other diseases. However, limited studies have been performed on the mechanism involved in the effect of C3G through transcriptome analysis. Thus, the objective of this study was to perform comparative transcriptome analysis of the spleen to determine gene expression profiles of wild-type mice (C57BL/6J Jms), an Alzheimer’s mouse model (APPswe/PS1dE9 mice), and a C3G-treated Alzheimer’s mouse model. Differentially expressed antioxidant, immune-related, and AD pathways genes were identified in the treated group. The validation of gene expression data via RT-PCR studies further supported the current findings. Six important antioxidant genes (S100a8, S100a9, Prdx2, Hp, Mpst, and Prxl2a) and a high number of immune-related genes were found to be upregulated in the treatment groups, suggesting the possible antioxidant and immunomodulatory mechanisms of C3G, respectively. Further studies are strongly recommended to elucidate the precise role of these essential genes and optimize the therapeutic function of C3G in AD and other disease conditions.

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Section: Discussionmentioning

confidence: 75%

Comparative Transcriptome Analysis of the Expression of Antioxidant and Immunity Genes in the Spleen of a Cyanidin 3-O-Glucoside-Treated Alzheimer’s Mouse Model

2021

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“…By investigating the underlying mechanisms of protective effects of FMT treatment on PD, this study also partially explains the mechanisms of the microbiota-gut-brain axis in the progression of PD. Although it is increasingly evident that the intestinal inflammation and barrier alterations are associated with neurodegeneration in multiple neurological disorders, including PD [ 39 , 94 ], AD [ 95 , 96 ], MS [ 97 ], and amyotrophic lateral sclerosis [ 98 ], specific pathways and mechanisms involved in the interaction between the gut and the CNS still remain unclear. Based on our current results, we speculate that the intestinal inflammation induced by bacterial elements through the LPS-activated TLR4/MyD88/NF-κB signaling pathway together with the following sustained and relatively severe disruption of the intestinal barrier that can leak pro-inflammatory factors into the circulation may contribute to neuroinflammation, ultimately leading to neurodegeneration in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

et al. 2021

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Background Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis. Results We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon. Conclusions Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis.

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“…Alzheimer's disease --in vivo: increased LPS [23] and zonulin levels in blood [24] Parkinson disease -ex vivo: augmented uptake of bacteria [2] in vivo: increased urinary secretion of probes [2]; increased blood zonulin levels [25] Major depression disorder --in vivo: increased permeability markers in blood, I-FABP and zonulin [26] Autism spectrum disorders in vivo: altered expression of tight junction proteins [27] in vivo: increased levels of zonulin [28,29] Many of the conditions associated with a leaky gut show signs of both increased paracellular and transcellular permeability. Moreover, new exciting findings connecting different conditions to a dysfunctional barrier by primarily in vivo biomarkers could potentially be complemented with other techniques to strengthen these findings.…”

Section: Uncategorized Permeability Changesmentioning

confidence: 99%

The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability

Schoultz

Keita

2020

Cells

243

222

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The intestinal barrier is essential in human health and constitutes the interface between the outside and the internal milieu of the body. A functional intestinal barrier allows absorption of nutrients and fluids but simultaneously prevents harmful substances like toxins and bacteria from crossing the intestinal epithelium and reaching the body. An altered intestinal permeability, a sign of a perturbed barrier function, has during the last decade been associated with several chronic conditions, including diseases originating in the gastrointestinal tract but also diseases such as Alzheimer and Parkinson disease. This has led to an intensified interest from researchers with diverse backgrounds to perform functional studies of the intestinal barrier in different conditions. Intestinal permeability is defined as the passage of a solute through a simple membrane and can be measured by recording the passage of permeability markers over the epithelium via the paracellular or the transcellular route. The methodological tools to investigate the gut barrier function are rapidly expanding and new methodological approaches are being developed. Here we outline and discuss, in vivo, in vitro and ex vivo techniques and how these methods can be utilized for thorough investigation of the intestinal barrier.

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C‐type lectin‐like receptor 2 and zonulin are associated with mild cognitive impairment and Alzheimer's disease

Cited by 32 publications

References 34 publications

Comparative Transcriptome Analysis of the Expression of Antioxidant and Immunity Genes in the Spleen of a Cyanidin 3-O-Glucoside-Treated Alzheimer’s Mouse Model

Comparative Transcriptome Analysis of the Expression of Antioxidant and Immunity Genes in the Spleen of a Cyanidin 3-O-Glucoside-Treated Alzheimer’s Mouse Model

Fecal microbiota transplantation protects rotenone-induced Parkinson’s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis

The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability

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