scholarly journals A37 ENTERIC MICROBIOTA CONTRIBUTE TO BEHAVIORAL ALTERATIONS OBSERVED IN MICE WITH COLITIS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 44-45
Author(s):  
F Vicentini ◽  
L Griffin ◽  
C Keenan ◽  
J Cavin ◽  
K Nieves ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Body Weight Loss ◽  
Sickness Behavior ◽  
Behavioral Changes ◽  
Brain Inflammation ◽  
Anxiety And Depression ◽  
Lipocalin 2 ◽  
Microbial Composition ◽  
Fecal Microbiota Transplant ◽  
Brain Physiology

Abstract Background The enteric microbiota has been recognized as an essential regulator of both gut and brain physiology, a complex interaction generally termed the microbiota-gut-brain axis. Disturbances to gastrointestinal physiology lead to alterations in the composition of the enteric microbiota, whereas dysbiosis can also contribute to pathophysiology. Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory conditions of the gastrointestinal tract, associated with microbial dysbiosis. Interestingly, IBD patients exhibit an increased incidence of mental illness (i.e. anxiety and depression), often termed “sickness behavior”, even during the remitting phase of their disease. Nevertheless, it is unclear if alterations in the enteric microbiota associated with IBD are responsible for the observed modification in brain function and behavior. Here, we hypothesized that sickness behavior is driven by alterations in microbial composition, which occur in the context of intestinal inflammation. Aims We sought to determine whether transfer of the microbiota from colitic mice, exhibiting sickness behaviour, into healthy counterparts would induce behavioral changes. Methods Male mice (C57Bl/6J; 8 weeks old) were used in all experiments. Colitis was induced by administration of 2.5% dextran sodium sulfate (DSS) in the drinking water for 5 days. Colonic inflammation was assessed by measuring fecal lipocalin-2 and the expression of pro-inflammatory mediators via qPCR. Cecal matter from donor mice (control or DSS treated) were collected for fecal microbiota transplant (FMT). FMT was performed via oral gavage in antibiotic-treated recipient mice. Gut bacteria were evaluated by 16S rRNA sequencing in cecal samples. Anxiety- and depression-like behavior were assessed by elevated plus maze and tail suspension test, respectively. Results DSS-treated mice exhibited clinical disease, reflected by body weight loss, increased fecal lipocalin-2 and elevated colonic pro-inflammatory cytokine transcripts. An increase in anxiety-like behavior was observed in mice with colitis, although no alterations in depression-like behavior were detected. Colitic mice exhibited a unique microbial community. Transferring cecal material from colitic mice into recipient, antibiotic-treated mice, recapitulated alterations in behavior seen in colitic donors, as shown by increased anxiety-like behavior and unexpectedly, increased depression-like behavior. These behavioral changes occurred in the absence of colonic or brain inflammation in the recipient mice, but were associated with changes in stress-related gene expression (i.e. Crh). Conclusions Colitis-associated sickness behavior can be transmitted to antibiotic-treated recipient mice via FMT, which occurs in the absence of overt intestinal or brain inflammation. Funding Agencies CIHRNational Council for Scientific and Technological Development (CNPq-Brazil)

scholarly journals Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice

2022 ◽  
Vol 23 (2) ◽  
pp. 920
Author(s):  
David Hutin ◽  
Karoline Alvik Hagen ◽  
Peng Shao ◽  
Kim Sugamori ◽  
Denis M. Grant ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Body Weight Loss ◽  
Mucosal Injury ◽  
Type I ◽  
Lipocalin 2 ◽  
Cytochrome P450 1A1 ◽  
Microbial Composition ◽  
Aryl Hydrocarbon ◽  
Significant Difference ◽  
Chemokine Ligand

Poly-ADP-ribose polymerases (PARPs) are important regulators of the immune system, including TCDD-inducible poly-ADP-ribose polymerase (TIPARP), also known as poly-ADP-ribose polymerase 7 (PARP7). PARP7 negatively regulates aryl hydrocarbon receptor (AHR) and type I interferon (IFN-I) signaling, both of which have been implicated in intestinal homeostasis and immunity. Since the loss of PARP7 expression increases AHR and IFN-I signaling, we used a murine dextran sulfate sodium (DSS)-induced colitis model to investigate the effect of PARP7 loss on DSS-induced intestinal inflammation. DSS-exposed Parp7−/− mice had less body weight loss, lower disease index scores, and reduced expression of several inflammation genes, including interleukin IL-6, C-x-c motif chemokine ligand 1 (Cxcl1), and lipocalin-2, when compared with wild-type mice. However, no significant difference was observed between genotypes in the colonic expression of the AHR target gene cytochrome P450 1A1 (Cyp1a1). Moreover, no significant differences in microbial composition were observed between the genotypes. Our findings demonstrate that the absence of PARP7 protein results in an impaired immune response to colonic inflammation and suggests that PARP7 may participate in the recruitment of immune cells to the inflammation site, which may be due to its role in IFN-I signaling rather than AHR signaling.

Behavioral Testing of Mice Concerning Anxiety and Depression

2015 ◽  
Vol 223 (3) ◽  
pp. 151-156 ◽  
Author(s):  
Nina Schweinfurth ◽  
Undine E. Lang
Keyword(s):  
Environmental Influences ◽  
Sickness Behavior ◽  
Laboratory Research ◽  
Anxiety And Depression ◽  
Housing Conditions ◽  
Human Beings ◽  
Behavioral Testing ◽  
New Developments ◽  
Animal Trials ◽  
Resilience Factors

Abstract. In the development of new psychiatric drugs and the exploration of their efficacy, behavioral testing in mice has always shown to be an inevitable procedure. By studying the behavior of mice, diverse pathophysiological processes leading to depression, anxiety, and sickness behavior have been revealed. Moreover, laboratory research in animals increased at least the knowledge about the involvement of a multitude of genes in anxiety and depression. However, multiple new possibilities to study human behavior have been developed recently and improved and enable a direct acquisition of human epigenetic, imaging, and neurotransmission data on psychiatric pathologies. In human beings, the high influence of environmental and resilience factors gained scientific importance during the last years as the search for key genes in the development of affective and anxiety disorders has not been successful. However, environmental influences in human beings themselves might be better understood and controllable than in mice, where environmental influences might be as complex and subtle. The increasing possibilities in clinical research and the knowledge about the complexity of environmental influences and interferences in animal trials, which had been underestimated yet, question more and more to what extent findings from laboratory animal research translate to human conditions. However, new developments in behavioral testing of mice involve the animals’ welfare and show that housing conditions of laboratory mice can be markedly improved without affecting the standardization of results.

scholarly journals The Gut–Brain Axis and Its Role in Controlling Eating Behavior in Intestinal Inflammation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 981
Author(s):  
Gordon William Moran ◽  
Gita Thapaliya
Keyword(s):  
Food Intake ◽  
Eating Behavior ◽  
Emotional Eating ◽  
Intestinal Inflammation ◽  
Cognitive Factors ◽  
Anxiety And Depression ◽  
Gut Peptides ◽  
Future Health ◽  
Inflammatory Bowel ◽  
Inflammatory Burden

Malnutrition represents a major problem in the clinical management of the inflammatory bowel disease (IBD). Presently, our understanding of the cross-link between eating behavior and intestinal inflammation is still in its infancy. Crohn’s disease patients with active disease exhibit strong hedonic desires for food and emotional eating patterns possibly to ameliorate feelings of low mood, anxiety, and depression. Impulsivity traits seen in IBD patients may predispose them to palatable food intake as an immediate reward rather than concerns for future health. The upregulation of enteroendocrine cells (EEC) peptide response to food intake has been described in ileal inflammation, which may lead to alterations in gut–brain signaling with implications for appetite and eating behavior. In summary, a complex interplay of gut peptides, psychological, cognitive factors, disease-related symptoms, and inflammatory burden may ultimately govern eating behavior in intestinal inflammation.

Behavior assessment and applications for BRD diagnosis: preweaned dairy calves

2020 ◽  
pp. 1-4
Author(s):  
Catie Cramer ◽  
Theresa L. Ollivett
Keyword(s):  
Clinical Signs ◽  
Sickness Behavior ◽  
Behavioral Changes ◽  
Dairy Calves ◽  
Detection Methods ◽  
Disease Detection ◽  
Test Characteristics ◽  
Behavioral Studies ◽  
Detection Program ◽  
Behavioral Assessments

Abstract Bovine respiratory disease (BRD) is an important disease in dairy calves due to its long-lasting effects. Early identification results in better outcomes for the animal, but producers struggle to identify all calves with BRD. Sickness behavior, or the behavioral changes that accompany illness, has been investigated for its usefulness as a disease detection tool. Behavioral changes associated with BRD include decreased milk intake and drinking speed, depressed attitude, and less likelihood of approaching a novel object or stationary human. Behavioral measurements are useful, as they can be collected automatically or with little financial input. However, one limitation of many BRD behavioral studies includes the use of either lung auscultation or clinical signs as reference methods, which are imperfect. Additionally, external factors may influence the expression of sickness behavior, which can affect if and when behavior can be used to identify calves with BRD. Behavioral measures available to detect BRD lack adequate sensitivity and specificity to be the sole means of disease detection, especially when detection tools, such as calf lung ultrasound, have better test characteristics. However, using behavioral assessments in addition to other detection methods can allow for a robust BRD detection program that can ameliorate the consequences of BRD.

scholarly journals Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease

2020 ◽  
Author(s):  
Yogesh Singh ◽  
Christoph Trautwein ◽  
Joan Romani ◽  
Madhuri S Salker ◽  
Peter H Neckel ◽  
...  
Keyword(s):  
Nervous System ◽  
Rat Model ◽  
Intestinal Inflammation ◽  
Short Chain Fatty Acids ◽  
Alpha Synuclein ◽  
Transgenic Rat ◽  
Microbial Composition ◽  
Specific Alteration ◽  
Metabolites Production ◽  
Transgenic Rat Model

AbstractSince Braak’s hypothesis stating that sporadic Parkinson’s disease follows a specific progression of the pathology from the peripheral to the central nervous system and can be monitored by detecting accumulation of the alpha-Synuclein protein. There is growing interest in understanding how the gut (commensal) microbiome can regulate alpha-Synuclein accumulation which can lead to PD. We studied a transgenic rat model overexpressing the human alpha-Synuclein and found that the protein overexpression resulted in gut alpha-Synuclein expression and aggregation in the gut neurons with advancing age. A progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young transgenic rat model and interestingly this ratio was then increased with aging. This observation was accompanied in older animals by intestinal inflammation, increase gut permeability and a robust alteration in metabolites production characterized by the increase of succinate level in the feces and serum. Manipulation of the gut bacteria by short-term antibiotics treatment revealed a complete loss of short-chain fatty acids (SCFAs) and reduction in succinate levels. Although antibiotics treatment did not change alpha-synuclein expression in the enteric nervous system of the colon, it can reduce alpha-synuclein expression in the olfactory bulb of the transgenic rats. In summary, synchronous with ageing, our data emphasize that the gut microbiome dysbiosis leads to a specific alteration of gut metabolites which are reflected in the serum and can be modulated by the environment.

scholarly journals P882 Dietary interventions may modify intestinal inflammation via altering microbial composition—a cross-over trial

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S563-S563
Author(s):  
L Godny ◽  
L Reshef ◽  
T Pfeffer-Gik ◽  
K Yadagar ◽  
K Zonensain ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Dietary Interventions ◽  
Microbial Composition

scholarly journals Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism

2018 ◽  
Vol 115 (43) ◽  
pp. 11036-11041 ◽  
Author(s):  
Yasuharu Nagahama ◽  
Mayuko Shimoda ◽  
Guoliang Mao ◽  
Shailendra Kumar Singh ◽  
Yuuki Kozakai ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Purine Metabolism ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Epithelial Regeneration ◽  
Mtorc1 Signaling ◽  
Inflammatory Bowel

Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.

Neuroimmunology: Behavioral Effects

2018 ◽  
Author(s):  
Gretchen N. Neigh ◽  
Mandakh Bekhbat ◽  
Sydney A. Rowson
Keyword(s):  
Immune System ◽  
Animal Studies ◽  
Social Withdrawal ◽  
Sickness Behavior ◽  
Behavioral Changes ◽  
Neural Pathways ◽  
Behavioral Alterations ◽  
Psychosocial Approaches ◽  
Sleep Alterations ◽  
Neuroimmune Activation

Bidirectional interactions between the immune system and central nervous system have been acknowledged for centuries. Over the past 100 years, pioneering studies in both animal models and humans have delineated the behavioral consequences of neuroimmune activation, including the different facets of sickness behavior. Rodent studies have uncovered multiple neural pathways and mechanisms that mediate anorexia, fever, sleep alterations, and social withdrawal following immune activation. Furthermore, work conducted in human patients receiving interferon treatment has elucidated some of the mechanisms underlying immune-induced behavioral changes such as malaise, depressive symptoms, and cognitive deficits. These findings have provided the foundation for development of treatment interventions for conditions in which dysfunction of immune-brain interactions leads to behavioral pathology. Rodent models of neuroimmune activation frequently utilize endotoxins and cytokines to directly stimulate the immune system. In the absence of pathogen-induced inflammation, a variety of environmental stressors, including psychosocial stressors, also lead to neuroimmune alterations and concurrent behavioral changes. These behavioral alterations can be assessed using a battery of behavioral paradigms while distinguishing acute sickness behavior from the type of behavioral outcome being assessed. Animal studies have also been useful in delineating the role of microglia, the neuroendocrine system, neurotransmitters, and neurotrophins in mediating the behavioral implications of altered neuroimmune activity. Furthermore, the timing and duration of neuroimmune challenge as well as the sex of the organism can impact the behavioral manifestations of altered neuroimmune activity. Finally, neuroimmune modulation through pharmacological or psychosocial approaches has potential for modulating behavior.

scholarly journals Behavioral and neurophysiological taste responses to sweet and salt are diminished in a model of subclinical intestinal inflammation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
David W. Pittman ◽  
Guangkuo Dong ◽  
Alexandra M. Brantly ◽  
Lianying He ◽  
Tyler S. Nelson ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Sickness Behavior ◽  
Taste Bud ◽  
Chorda Tympani Nerve ◽  
Inflammatory Conditions ◽  
Taste Changes ◽  
Infection And Inflammation ◽  
Inflammatory Bowel ◽  
Fat Feeding

Abstract There is strong evidence for gut-taste bud interactions that influence taste function, behavior and feeding. However, the effect of gut inflammation on this axis is unknown despite reports of taste changes in gastrointestinal (GI) inflammatory conditions. Lipopolysaccharide (LPS), an inflammatory stimulus derived from gram-negative bacteria, is present in the normal GI tract and levels increase during high-fat feeding and gut infection and inflammation. Recordings from the chorda tympani nerve (CT), which transmits taste information from taste buds on the anterior tongue to the brain, previously revealed a transient decrease in sucrose responses in mice that ingest LPS during a single overnight period. Here we test the effect of acute or chronic, weekly LPS gavage on licking behavior and CT responses. Using brief-access testing, rats treated with acute LPS and mice receiving acute or chronic LPS decreased licking responses to sucrose and saccharin and to NaCl in mice. In long-term (23 h) tests chronic LPS also reduced licking responses to saccharin, sucrose, and NaCl in mice. Neurophysiological recordings from the CT supported behavioral changes, demonstrating reduced responses to sucrose, saccharin, acesulfame potassium, glucose and NaCl in acute and chronic LPS groups compared to controls. Chronic LPS significantly elevated neutrophils in the small intestine and colon, but LPS was not detected in serum and mice did not display sickness behavior or lose weight. These results indicate that sweet and salt taste sensitivity could be reduced even in asymptomatic or mild localized gut inflammatory conditions such as inflammatory bowel disease.

scholarly journals Ameliorative Effect of Sinapic Acid on Dextran Sodium Sulfate- (DSS-) Induced Ulcerative Colitis in Kunming (KM) Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bo Qian ◽  
Chengqiang Wang ◽  
Zhen Zeng ◽  
Yuan Ren ◽  
Dayu Li ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Intestinal Inflammation ◽  
Gastrointestinal Disease ◽  
Sinapic Acid ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Inflammatory Cells ◽  
Wall Thickening ◽  
Mrna Levels ◽  
Km Mice

Ulcerative colitis is a chronic gastrointestinal disease characterized by intestinal inflammation and serious mucosal damage. As a naturally hydroxycinnamic acid, sinapic acid (SA) has antioxidant, anticancer, and neuroprotective activities. We investigated the anticolitic effect and potential mechanisms of SA in DSS-induced colitis in Kunming (KM) mice. SA treatment significantly reduced body weight loss, colon shortening, and intestinal wall thickening in colitis mice. SA treatment also significantly reduced the histological infiltration of inflammatory cells and decreased myeloperoxidase (MPO) activity in the colons of colitis mice. The administration of SA attenuated oxidative damage by enhancing the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase and reduced the serum and colonic mRNA levels of proinflammatory cytokines in colitis mice. We used qRT-PCR and Western blotting assays and demonstrated that SA reduced the activation of the NLRP3 inflammasome and attenuated intestinal permeability by enhancing the expression of ZO-1, occludin, and claudin-1 in colitis mice. Here, we conclude that SA exhibits great anticolitic activity against DSS-induced colitis by enhancing the activity of antioxidant enzymes, reducing intestinal inflammation, and maintaining the intestinal barrier. Finally, we suggest that SA may be a safe adjuvant for the prevention of clinical colitis.

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