The Role of Gut Microbiota in Chronic Itch-Evoked Novel Object Recognition-Related Cognitive Dysfunction in Mice

Li, Yujuan; Zhang, Wencui; Sun, Tainning; Liu, Baowen; Manyande, Anne; Xu, Weiguo; Xiang, Hongyu

doi:10.3389/fmed.2021.616489

Cited by 8 publications

(15 citation statements)

References 51 publications

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“…However, a decrease in the serotonin level also causes cognitive deterioration. Previous studies indicated that serotonergic neuron has a primary role in cognition (Sun et al, 2021;Shine et al, 2022). The alternation of the 5-HT neuron system significantly affects NCDs.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Liu

Sun

et al. 2022

Front. Microbiol.

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Neurocognitive disorders (NCDs) include complex and multifactorial diseases that affect many patients. The 5-hydroxytryptamine (5-HT) neuron system plays an important role in NCDs. Existing studies have reported that para-chlorophenylalanine (PCPA), a 5-HT scavenger, has a negative effect on cognitive function. However, we believe that PCPA may result in NCDs through other pathways. To explore this possibility, behavioral tests were performed to evaluate the cognitive function of PCPA-treated mice, suggesting the appearance of cognitive dysfunction and depression-like behavior. Furthermore, 16S rRNA and metabolomic analyses revealed that dysbiosis and acetate alternation could be related to PCPA-induced NCDs. Our results suggest that not only 5-HT depletion but also dysbiosis and acetate alternation contributed to PCPA-related NCDs. Specifically, the latter promotes NCDs by reducing short-chain fatty acid levels. Together, these findings provide an alternative perspective on PCPA-induced NCDs.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Liu

Sun

et al. 2022

Front. Microbiol.

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“…The significance testing was two-tailed, and p < 0.05 was statistically significant. The rats that underwent the SMIR surgery were divided into the susceptible group (cognitively compromised pain rats) and the unsusceptible group (cognitively normal pain rats) based on the Ward method and Euclidean distance square as distance measurement using the hierarchical cluster analysis of the data from the novel object recognition test and the Y-maze test [ 31 ]. Statistical analyses and graphs (except the 16S rRNA microbiome sequencing analyses) were performed with the Adobe Illustrator Artwork 14.0 and GraphPad Prism 8.0.…”

Section: Methodsmentioning

confidence: 99%

“…To generate the pseudo-germ-free animal model, we provided the experimental rats with vancomycin hydrochloride (500 mg/L), ampicillin sulfate (1 g/L), neomycin sulfate (1 g/L), and metronidazole (1 g/L) in their sterile drinking water for 2 weeks [9,31]. Each mixed fecal sample (1 g) from different unsusceptible or susceptible rats was suspended in 10 mL of sterile phosphate-buffered saline and vigorously vortexed for 5 min.…”

Section: Microbiota Depletion and Fmtmentioning

confidence: 99%

“…Each mixed fecal sample (1 g) from different unsusceptible or susceptible rats was suspended in 10 mL of sterile phosphate-buffered saline and vigorously vortexed for 5 min. The suspensions were obtained after homogenization and centrifugation to colonize pseudo-germ-free rats [9,31]. Regarding the European Consensus Conference for fecal microbiota transplantation in clinical practice [32,33], 0.43 g of feces/kg body weight is recommended, and, accordingly, a 200 g rat should receive 0.86 g feces diluted in 0.86 mL PBS via gavage once a day for 2 consecutive weeks.…”

Section: Microbiota Depletion and Fmtmentioning

confidence: 99%

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SCFAs Ameliorate Chronic Postsurgical Pain–Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats

Sun

et al. 2022

Mol Neurobiol

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Patients with chronic postsurgical pain (CPSP) frequently exhibit comorbid cognitive deficits. Recent observations have emphasized the critical effects of gut microbial metabolites, like short-chain fatty acids (SCFAs), in regulating cognitive function. However, the underlying mechanisms and effective interventions remain unclear. According to hierarchical clustering and 16S rRNA analysis, over two-thirds of the CPSP rats had cognitive impairment, and the CPSP rats with cognitive impairment had an aberrant composition of gut SCFA-producing bacteria. Then, using feces microbiota transplantation, researchers identified a causal relationship between cognitive-behavioral and microbic changes. Similarly, the number of genera that generated SCFAs was decreased in the feces from recipients of cognitive impairment microbiota. Moreover, treatment with the SCFAs alleviated the cognitive-behavioral deficits in the cognitively compromised pain rats. Finally, we observed that SCFA supplementation improved histone acetylation and abnormal synaptic transmission in the medial prefrontal cortex (mPFC), hippocampal CA1, and central amygdala (CeA) area via the ACSS2 (acetyl-CoA synthetase2)-HDAC2 (histone deacetylase 2) axis. These findings link pain-related cognition dysfunction, gut microbiota, and short-chain fatty acids, shedding fresh insight into the pathogenesis and therapy of pain-associated cognition dysfunction.

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“…Fecal samples were collected immediately after defecating in a sterilized centrifuge tube. The filter paper was changed after each mouse as our previously study ( Li et al, 2021 ). Fecal samples were stored in a − 80°C freezer.…”

Section: Methodsmentioning

confidence: 99%

The Role of Gut Microbiota in Mice With Bile Duct Ligation-Evoked Cholestatic Liver Disease-Related Cognitive Dysfunction

et al. 2022

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The pathogenesis of Hepatic Encephalopathy (HE) is complex and multifactorial. The development of metagenomics sequencing technology led to show the significant role of gut microbiota in the pathogenesis of cognitive dysfunction, which paved the way for further research in this field. However, it is unknown whether gut microbiota plays a role in bile duct ligation (BDL)-evoked cholestatic liver disease-related cognitive dysfunction. The aim of this investigation is to assess BDL mice induced cognitive dysfunction and meanwhile to delineate the alteration of gut microbiota in cognitive dysfunction mice, which may underline the role of gut microbiota in BDL mice induced cognitive dysfunction. Our study was carried out in male C57BL/6 J mice with bile duct ligation. The liver functions were assessed via different biochemical markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and total bile acid (TBA)] and a histopathological examination of the liver tissue. We used the novel object recognition test (NORT) to assess cognitive dysfunction. And BDL mice were divided into BDL with cognitive dysfunction (BDL-CD) or BDL without cognitive dysfunction (BDL-NCD groups) by the result of hierarchical cluster analysis of NORT. Then, 16S ribosomal RNA (rRNA) gene sequencing was used to compare the gut bacterial composition between BDL-CD and BDL-NCD groups. According to our results, we concluded that bile duct ligation can significantly change the gut microbiota composition, and Bacteroides fragilis, Bacteroides ovatus V975, and Bacteroides thetaiotaomicron play a vital role in BDL-evoked cholestatic liver disease-related cognitive dysfunction.

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The Role of Gut Microbiota in Chronic Itch-Evoked Novel Object Recognition-Related Cognitive Dysfunction in Mice

Cited by 8 publications

References 51 publications

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders

SCFAs Ameliorate Chronic Postsurgical Pain–Related Cognition Dysfunction via the ACSS2-HDAC2 Axis in Rats

The Role of Gut Microbiota in Mice With Bile Duct Ligation-Evoked Cholestatic Liver Disease-Related Cognitive Dysfunction

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