Effect of dietary palm oil on growth and carcass composition of Heterobranchus longifilis fingerlings

This study investigated the effects of dietary palm oil (PO) on growth performance and carcass composition of Heterobranchus longifilis with the goal of replacing dietary fish oil with palm oil. In this study triplicate groups of H. longifilis fingerlings were fed the experimental diets for 8 weeks. Five isonitrogenous (45% crude protein), isoenergetic (20 KJg-1) experimental diets were made containing either 6.0% FO and 0% PO, 4.5% FO and 1.5% PO; 3.0% FO and 3.0% PO; 1.5% FO and 4.5% PO; or 0% FO and 6.0% PO using soybean and fish meal as the protein source. Dietary palm oil had no significant effect on growth rate or feed conversion ratio. Similarly, No significant differences were observed between dietary treatments for moisture, protein and ash content in H. longifilis fingerlings. However, fillet saturated, monounsaturated fatty acids and liver lipid deposition were significantly (P0.05) higher in fish fed 6.0% PO diet. This study suggests that the replacement of cod liver oil by palm oil as lipid supplement in the diet permitted a clear improvement of growth and FCR of H. longifilis. This indicates that PO can effectively replace FO in the diet of the fish without compromising fish growth and feed efficiency

Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice

Stimulator of interferon genes (STING) is activated after detection of cytoplasmic dsDNA by cGAS (cyclic GMP-AMP synthase) as part of the innate immunity defence against viral pathogens. STING binds TANK-binding kinase 1 (TBK1). TBK1 mutations are associated with familial amyotrophic lateral sclerosis, and the STING pathway has been implicated in the pathogenesis of further neurodegenerative diseases. To test whether STING activation is sufficient to induce neurodegeneration, we analysed a mouse model that expresses the constitutively active STING variant N153S. In this model, we focused on dopaminergic neurons, which are particularly sensitive to stress and represent a circumscribed population that can be precisely quantified. In adult mice expressing N153S STING, the number of dopaminergic neurons was smaller than in controls, as was the density of dopaminergic axon terminals and the concentration of dopamine in the striatum. We also observed alpha-synuclein pathology and a lower density of synaptic puncta. Neuroinflammation was quantified by staining astroglia and microglia, by measuring mRNAs, proteins and nuclear translocation of transcription factors. These neuroinflammatory markers were already elevated in juvenile mice although at this age the number of dopaminergic neurons was still unaffected, thus preceding the degeneration of dopaminergic neurons. More neuroinflammatory markers were blunted in mice deficient for inflammasomes than in mice deficient for signalling by type I interferons. Neurodegeneration, however, was blunted in both mice. Collectively, these findings demonstrate that chronic activation of the STING pathway is sufficient to cause degeneration of dopaminergic neurons. Targeting the STING pathway could therefore be beneficial in Parkinson’s disease and further neurodegenerative diseases

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of the cellular pathologies associated are still elusive, complicating the development of effective therapeutic strategies. Combining molecular genetics with target-based approaches, we established that glycation, an unavoidable age-associated post-translational modification, enhanced α-synuclein toxicity in vitro and in vivo, in Drosophila and in mice. Glycation affected primarily the N-terminal region of α-synuclein, reducing membrane binding, impaired the clearance of α-synuclein, and promoted the accumulation of toxic oligomers that impaired neuronal synaptic transmission. Strikingly, using glycation inhibitors, we demonstrated that normal clearance of α-synuclein was re-established, aggregation was reduced, and motor phenotypes in Drosophila were alleviated. Altogether, our study demonstrates glycation constitutes a novel drug target that can be explored in synucleinopathies as well as in other neurodegenerative conditions.Authors were supported by: H.V.M. (Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT), Portugal SFRH/BPD/64702/ 2009 and SFRH/BPD/109347/2015; EU FP7 project MEFOPA), L.M.A.O (FCT - SFRH/BD/23604/2005; CIRM-BMFB joint grant, 315050 AZ0101-31P6855), R.M.O. and T.S. (FCT SFRH/BPD/41416/2007; SFRH/ BPD/31209/2006); W.X. (Deutsche Forschungsgemeinschaft, SFB539/A3); C.B. and F.G. (Parkinson’s UK and the Medical Research Council, UK). S.E. is supported by Israel Academy of Sciences, Rappaport Family Institute for Research in the Medical Sciences, The Allen and Jewel Prince Center for Neurodegenerative Disorders of the Brain. T.F.O. (EMBO Installation Grant; Marie Curie IRG, Neurofold; DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain; I.C.M. (FCT SFRH/BPD/74287/2010; Investigador FCT IF/00772/ 2013). This work was supported by: FCT PTDC/SAUNEU/ 105215/2008, PTDC/QUI/73430/2006, PTDC/SAUENB/ 117013/2010, PTDC/NEU-OSD/5644/2014; EU FP7 project MEFOPA; CIRM-BMFB joint grant (315050 AZ0101-31P6855); Max Planck Society; and European Union (NEURASYNC PITNGA-2009-238316).info:eu-repo/semantics/publishedVersio