Role of liraglutide in Alzheimer's disease pathology

Background The described relationship between Alzheimer's disease (AD) and type 2 diabetes (T2D) and the fact that AD has no succesful treatment has led to the study of antidiabetic drugs that may limit or slow down AD pathology. Main body Although T2D treatment has evident limitations, options are increasing including glucagon-like peptide 1 analogs. Among these, liraglutide (LRGT) is commonly used by T2D patients to improve beta cell function and suppress glucagon to restore normoglycaemia. Interestingly, LRGT also counterbalances altered brain metabolism and has anti-inflammatory properties. Previous studies have reported its capacity to reduce AD pathology, including amyloid production and deposition, tau hyperphosphorylation, or neuronal and synaptic loss in animal models of AD, accompanied by cognitive improvement. Given the beneficial effects of LRGT at central level, studies in patients have been carried out, showing modest beneficial effects. At present, the ELAD trial (Evaluating Liraglutide in Alzheimer's Disease NCT01843075) is an ongoing phase IIb study in patients with mild AD. In this minireview, we resume the outcomes of LRGT treatment in preclinical models of AD as well as the available results in patients up to date. Conclusion The effects of LRGT on animal models show significant benefits in AD pathology and cognitive impairment. While studies in patients are limited, ongoing clinical trials will probably provide more definitive conclusions on the role of LRGT in AD patients

Periodontitis induced by bacterial infection exacerbates features of Alzheimer\u27s disease in transgenic mice.

Periodontitis is a localized infectious disease caused by periodontopathic bacteria,such as Porphyromonas gingivalis. Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer’s disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis-inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalismay exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation

The proximate composition of three marine pelagic fish: blue whiting (Micromesistius poutassou), boarfish (Capros aper) and Atlantic herring (Clupea harengus)

peer reviewedThis study presents data from an in-depth proximate compositional analysis of three marine fish species: blue whiting (Micromesistius poutassou), boarfish (Capros aper) and Atlantic herring (Clupea harengus). These fish contained significant amounts of protein (16–17%), lipids (4–11%) and minerals (2–6% ash). The proteins, particularly from boarfish, had close to optimum amino acid profiles for human and fish nutrition. They compared favourably with other fish species in terms of total lipids and relative concentration of the omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid (11.8–13.3% and 5.9–8.1% in triacylglycerols [TG] and 24.6–35.4% and 5.8–12.0% in phospholipids [PL]). Atlantic herring had the highest lipid content among the three fish and was found to contain high levels of PL poly-unsaturated fatty acids, including omega-3 fatty acids. Minerals detected in the fish included calcium (272–1,520 mg/100 g), phosphorus (363–789 mg/100 g), iron (1.07–2.83 mg/100 g), magnesium (40.70–62.10 mg/100 g), potassium (112.00–267.00 mg/100 g), selenium (0.04–0.06 mg/100 g), sodium (218.00–282.00 mg/100 g) and zinc (1.29–5.57 mg/100 g). Boarfish had the highest ash fraction and also the highest levels of all the minerals, except potassium. Atlantic herring had considerably lower mineral content compared with the other two species and, levels detected were also lower than those reported in previously published studies. Heavy metals contents were quantified, and levels were significantly below the maximum allowable limits for all elements except arsenic, which ranged from 1.34 to 2.44 mg/kg in the three fish species. Data outlined here will be useful for guiding product development. Future studies would benefit from considering catch season, sex and developmental stage of the fish

Adolescent girls in romantic relationship under child protection system – Issues and concerns: A study from India

Background: Existing literature shows the developmental significance of romantic relationships during adolescence and its influence on mental health and emotional well-being of adolescents. However, in recent years, this phenomenon has begun to receive more research attention in the Indian context. In India, many adolescent girls engage in risk-taking behaviors such as running away from home, child marriage, unsafe sexual relationships and teenage pregnancy, and consequently come into contact with child protection units. Methods: Adopting a retrospective exploratory research design, this study is a case report analysis of the psychosocial issues at individual level and family level in romantic relationship of adolescent girls who engaged in such risk-taking behaviors and were institutionalized in a State Children's Home in urban India. Results: In the present study, the mean age of the participants was 16.34 years with the range of 14–18 years. About 60% of the participants were in high school. Majority of them hailed from nuclear family with lower socioeconomic status and belonged to Hindu Religion. Psychosocial issues among adolescents and parents before and after risk-taking behaviors are varied and interlinked. Majority of the issues are related to the social norms and have significant impact on adolescents and their parents. Conclusion: Implications for future research, and for designing interventions for adolescents and their families, based on a mental health and development perspective, are highlighted. There is a need for enhancing skills among adolescent girls and for family interventions to enhance parent–children relationships to deal effectively with issues in the context of adolescent romantic relationships

Blue whiting (Micromesistius poutassou) muscle protein hydrolysate with in vitro and in vivo antidiabetic properties

A blue whiting (Micromesistius poutassou) protein hydrolysate generated using Alcalase 2.4L and Flavourzyme 500L and its simulated gastrointestinal digestion (SGID) sample was assessed for antidiabetic potential in vitro and in vivo. In addition to inhibiting dipeptidyl peptidase-IV (DPP–IV), the hydrolysates mediated insulin and glucagon-like peptide-1 (GLP-1) release from BRIN-BD11 and GLUTag cells, respectively. No significant difference was observed in insulinotropic and DPP-IV inhibitory activity following SGID, while GLP-1 secretion increased significantly (p < 0.01). SGID resulted in a significant increase in membrane potential, intracellular calcium and cyclic AMP concentration (p < 0.001) versus a glucose control, indicating that insulin secretion may be mediated by the KATP channel-dependent and the protein kinase A pathways. Additionally, acute (90–120min) and persistent (4h) glucose-lowering effects of the blue whiting hydrolysate were observed in normal healthy mice. These results demonstrate that the blue whiting protein hydrolysate had significant metabolic effects relevant to glucose control in vivo.Department of Agriculture, Food and the Marine, Ireland under grant numbers 11/F/063, 11/F/064, 13/F/467, 13/F/536 and 14/F/873, Department of Employment and Learning (DEL), Science Foundation Ireland Infrastructure Fund, Higher Education Authorit

Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: a source of antidiabetic peptides

Large quantities of low-value protein rich co-products, such as salmon skin and trimmings, are generated annually. These co-products can be upgraded to high-value functional ingredients. The aim of this study was to assess the antidiabetic potential of salmon skin gelatin and trimmings-derived protein hydrolysates in vitro. The gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L exhibited significantly higher (p < 0.001) insulin and GLP-1 secretory activity from pancreatic BRIN-BD11 and enteroendocrine GLUTag cells, respectively, when tested at 2.5 mg/mL compared to hydrolysates generated with Alcalase 2.4L or Promod 144MG. The gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L showed significantly more potent (p < 0.01) DPP-IV inhibitory activity than those generated with Alcalase 2.4L or Promod 144MG. No significant difference was observed in the insulinotropic activity mediated by any of the trimmings-derived hydrolysates when tested at 2.5 mg/mL. However, the trimmings hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L exhibited significantly higher DPP-IV inhibitory (p < 0.05:Alcalase 2.4L and p < 0.01:Promod 144MG) and GLP-1 (p < 0.001, 2.5 mg/mL) secretory activity than those generated with Alcalase 2.4L or Promod 144MG. The salmon trimmings hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L when subjected to simulated gastrointestinal digestion (SGID) was shown to retain its GLP-1 secretory and DPP-IV inhibitory activities, in addition to improving its insulin secretory activity. However, the gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L was shown to lose GLP-1 secretory activity following SGID. A significant increase in membrane potential (p < 0.001) and intracellular calcium (p < 0.001) by both co-product hydrolysates generated with Alcalase 2.4L and Flavourzyme 500L suggest that both hydrolysates mediate their insulinotropic activity through the KATP channel-dependent pathway. Additionally, by stimulating a significant increase in intracellular cAMP release (p < 0.05) it is likely that the trimmings-derived hydrolysate may also mediate insulin secretion through the protein kinase A pathway. The results presented herein demonstrate that salmon co-product hydrolysates exhibit promising in vitro antidiabetic activity