Prebiotics modulate the microbiota-gut-brain axis and ameliorate anxiety and depression-like behavior in HFD-fed mice.

Previous research has demonstrated that Prebiotics can influence the composition of the gut microbiota, consequently impacting mood regulation. This study aimed to assess the effects of Prebiotics, specifically Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on neuroinflammation, depression, and anxiety-like behavior in a mouse model fed a high-fat diet (HFD). Initially, mice were divided into two groups: a control group on a standard diet (n = 15) and a group on an HFD for 18 weeks (n = 45). By the 13th week, the HFD group was further divided into experimental groups: Control (n = 15), HFD (n = 15), HFD receiving Prebiotics (n = 15), and HFD receiving Fluoxetine (n = 15). From the 13th week onward, the HFD + Prebiotics group received both the high-fat diet and a combination of FOS and GOS, while the HFD + Fluoxetine group received Fluoxetine in their drinking water. In the 18th week, all mice underwent tests to evaluate behavior, including the Tail Suspension Test (TST), Forced Swimming Test (FST), Sucrose Preference Test (SPT), and the Plus Maze Test (PMT), after which they were euthanized. Mice on the HFD exhibited increased body weight, abdominal size, blood glucose, triglyceride levels, cholesterol, insulin, HOMA index, and higher serum IL-1ß. These obese mice also displayed an increased number of microglia and astrocytes, activation of the TLR4 pathway, and elevated levels of neuroinflammatory markers like TNF-α, IL-1ß, and COX-2. Moreover, obese mice showed increased activation of the IDO pathway and decreased levels of NMDA receptors. Additionally, markers of neurogenesis and synaptic plasticity, such as PSD, SAP 102, CREB-p, and BDNF, were lower. Treatment with FOS and GOS reversed symptoms of depression and anxiety in mice subjected to HD. This improvement in behavior resulted from a reduction in dysbiosis with an increase in acetate-producing bacteria (B. acidifaciens and B. dorei) and intestinal permeability, leading to a decrease in chronic peripheral and central inflammation. Furthermore, the modulation of the gut-brain axis by FOS and GOS promoted elevated acetate and GPR43 levels in the brain and a reduction in the levels of pro-inflammatory cytokines, positively impacting signaling pathways of neuronal proliferation and survival in the hippocampus and prefrontal cortex.

Fructooligosaccharides and galactooligosaccharides improve hepatic steatosis via gut microbiota-brain axis modulation.

Studies have shown that gut dysbiosis is associated with the steatotic liver disease associated with metabolic dysfunction (MALSD) and its severity. This study evaluated the effects of two commercially available prebiotics fructooligosaccharides (FOS) and galactooligosaccharides(GOS) on hepatic adipogenesis, inflammation, and gut microbiota in high-fat diet-induced MALSD. The results indicated that FOS and GOS effectively reduced insulin resistance, hyperglycaemia, triglyceridemia, cholesterolaemia, and IL-1ß serum levels. Moreover, FOS and GOS modulated the lipogenic (SREBP-1c, ACC, and FAS) and lipolytic (ATGL) signalling pathways, and reduced inflammatory markers such as p-NFκB-65, IL-6, iNOS, COX-2, TNF-α, IL-1ß, and nitrotyrosine. FOS and GOS also enhanced the abundance of acetate producers' bacteria Bacteroides acidifaciens and Bacteroides dorei. FOS and GOS also induced positive POMC/GPR43 neurons at the arcuate nucleus, indicating hypothalamic signalling modulation. Our results suggest that FOS and GOS attenuated MALSD by reducing the hepatic lipogenic pathways and intestinal permeability through the gut microbiota-brain axis.

Metformin and fluoxetine improve depressive-like behavior in a murine model of Parkinsons disease through the modulation of neuroinflammation, neurogenesis and neuroplasticity.

Thereabout 30-40% of patients with Parkinson's Disease (PD) also have depression contributing to the loss of quality of life. Among the patients who treat depression, about 50% do not show significant improvement due to the limited efficacy of the treatment. So far, there are no effective disease-modifying treatments that can impede its progression. The current clinical approach is based on symptom management. Nonetheless, the reuse of drugs with excellent safety profiles represents an attractive alternative strategy for treating of different clinical aspects of PD. In this study, we evaluated the effects of metformin separately and associated with fluoxetine on depressive like-behavior and motor alterations in experimental Parkinson's disease. C57BL6 mice were induced with rotenone (2.5 mg/kg/day) for 20 days and treated with metformin (200 mg/kg/day) and fluoxetine (10 mg/kg/day) from the 5th day of induction. The animals were submitted to Sucrose Preference, Tail Suspension, and rotarod tests. Hippocampus, prefrontal cortex, and substantia nigra were dissected for molecular and morphological analysis. Metformin and fluoxetine prevented depressive-like behavior and improved motor impairment and increased TH nigral positive cells. Metformin and fluoxetine also reduced IBA-1 and GFAP positive cells in the hippocampus. Moreover, metformin reduced the phospho-NF-kB, IL-1ß in the prefrontal cortex and iNOS levels in the hippocampus. Both metformin and fluoxetine increased neurogenesis by increasing KI67, but only the combined treatment increased neuronal survival by NeuN positive cells in the hippocampus. In addition, fluoxetine reduced cell death, decreasing caspase-3 and PARP-1 levels. Lastly, metformin potentiated the effect of fluoxetine on neuroplasticity by increasing BDNF positive cells. Metformin has antidepressant and antiparkinsonian potential due to anti-inflammatory neurogenic, and neuroplasticity-inducing effects when combined with fluoxetine.

Does physical exercise influence in the development of neuroeschistosomiasis?

Neuroschistosomiasis is a severe form of presentation of schistosomiasis in which Schistosoma spp. affects the central nervous system. This is the first study performed to analyze whether there is any relationship between physical effort and the appearance of neuroschistosomiasis, through clinical, molecular and immunological evaluations. An experimental controlled study using 64 male Balb/c inbred mice divided into four groups according to presence or absence of S. mansoni infection and submitted to physical effort or resting was conducted. Thirteen weeks after exercise training, S. mansoni DNA was detected in the brain or spinal cord in about 30% of the infected animals moreover, only S. mansoni-positive samples showed positive labeling for S. mansoni antigens in the brain or spinal cord, with a striking reaction inside the microglia. However, the behavioral tests did not show any clinical symptoms of neuroschistosomiasis in animals submitted to physical effort or in resting. In animals with S. mansoni-positive DNA, immunohistochemical data revealed astrogliosis and microgliosis, elevated IL-10 levels and decreased TNF-α expression. This study demonstrated that isometric exercise does not promote neuroschistosomiasis, furthermore, ectopic forms of schistosomiasis in the central nervous system were largely asymptomatic and exhibited a Th2 immune response profile. More experimental studies are necessary in order to characterize the pathological process of experimental neuroschistosomiasis.

Mesenteric ischemia as a cause of early death among mice infected by Schistosoma mansoni

Laboratory maintenance of the Schistosoma mansoni cycle is necessary for developing studies regarding the diagnosis, treatment and control of schistosomiasis. Within this perspective, it is paramount that mice infected by the parasite should present a minimum survival of six months. However, between October 2016 and May 2017, early deaths were observed among infected animals kept in the vivarium of the Schistosomiasis Reference Service of IAMFIOCRUZ. Therefore, the purpose of the present study was to present the results obtained after investigating the main cause of death among these animals. To achieve this, animals that died or that needed to be euthanized due to clinical distress caused by parasite infection were necropsied to investigate the cause of death and clinical condition. Fragments from the intestines, mesenteric vessels and livers were removed and were subjected to histopathological studies. In addition, mouse feces were collected and analyzed using the hydrogen peroxide reaction to detect occult blood. Over an eight-month period, 70 deaths were noted. Forty two animals presented mesenteric ischemia, a vascular insufficiency syndrome that causes a reduction in the nutrient supply to the intestinal viscera. There is, therefore, a need to reduce the infective parasite load in mice to increase their survival, reduce distress caused by the infection and ensure maintenance of the S. mansoni cycle, thus enabling continuity of scientific studies on this parasitosis.