Psychoactive Pharmaceuticals Induce Fish Gene Expression Profiles Associated with Human Idiopathic Autism

Idiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antidepressants by pregnant women has been associated with autism. These and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been found in drinking water from surface sources, providing another possible exposure route and raising questions about human health consequences. Here, we examined gene expression patterns of fathead minnows treated with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine & carbamazepine) in dosages intended to be similar to the highest observed conservative estimates of environmental concentrations. We conducted microarray experiments examining brain tissue of fish exposed to individual pharmaceuticals and a mixture of all three. We used gene-class analysis to test for enrichment of gene sets involved with ten human neurological disorders. Only sets associated with idiopathic autism were unambiguously enriched. We found that UPPs induce autism-like gene expression patterns in fish. Our findings suggest a new potential trigger for idiopathic autism in genetically susceptible individuals involving an overlooked source of environmental contamination

Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition

Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterized by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defense, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted

Effect of fruit extract of Fragaria vesca L. on experimentally induced inflammatory bowel disease in albino rats

AIM: Ulcerative colitis and Crohn’s disease are chronic recurrent inflammatory bowel disease (IBD) of unknown origin. Oxidative stress is believed to be a key factor in the pathogenesis and perpetuation of the mucosal damage in IBD. MATERIALS AND METHODS: Ethanolic extract of Fragaria vesca (EFFV) fruits was prepared by percolation method and subjected to oral toxicity testing using OECD guidelines. Albino rats were pretreated orally for 5 days with 3% gum acacia in control, EFFV 500 mg/kg in test and 5-aminosalisylic acid (5-ASA) 100 mg/kg in standard groups. Colitis was induced by transrectal administration of 4% acetic acid on 5(th) day. All the animals were sacrificed with ether overdose 48 hours after colitis induction, and 10 cm colon segment was resected from proximal end. Colon was weighed (for disease activity index) and scored macroscopically and microscopically after histological staining. Biochemical assessments included myeloperoxidase (MPO) and tissue catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD) measurements. Statistical analysis was done using one-way analysis of variance (ANOVA) followed by Dunnett’s “t” test. RESULTS: EFFV showed significant (P < 0.05) prevention of increase in colon weight and disease activity index along with decrease in macroscopic and microscopic lesion score as compared to control group. Significant improvement was observed in the levels of MPO, CAT and SOD, except GSH (P < 0.05). However, the effect of EFFV was significantly less than 5-ASA (P < 0.05). CONCLUSIONS: EFFV at 500 mg/kg showed significant amelioration of experimentally induced IBD, which may be attributed to its antioxidant and anti-inflammatory properties

Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas

Notch signaling regulates numerous developmental processes, often acting either to promote one cell fate over another or else to inhibit differentiation altogether. In the embryonic pancreas, Notch and its target gene Hes1 are thought to inhibit endocrine and exocrine specification. Although differentiated cells appear to downregulate Hes1, it is unknown whether Hes1 expression marks multipotent progenitors, or else lineage-restricted precursors. Moreover, although rare cells of the adult pancreas express Hes1, it is unknown whether these represent a specialized progenitor-like population. To address these issues, we developed a mouse Hes1CreERT2 knock-in allele to inducibly mark Hes1+ cells and their descendants. We find that Hes1 expression in the early embryonic pancreas identifies multipotent, Notch-responsive progenitors, differentiation of which is blocked by activated Notch. In later embryogenesis, Hes1 marks exocrine-restricted progenitors, in which activated Notch promotes ductal differentiation. In the adult pancreas, Hes1 expression persists in rare differentiated cells, particularly terminal duct or centroacinar cells. Although we find that Hes1+ cells in the resting or injured pancreas do not behave as adult stem cells for insulin-producing beta (β)-cells, Hes1 expression does identify stem cells throughout the small and large intestine. Together, these studies clarify the roles of Notch and Hes1 in the developing and adult pancreas, and open new avenues to study Notch signaling in this and other tissues