No abstract

DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+, a mitochondrial complex I inhibitor shown to induce dopaminergic cells death. In a global label-free proteomics analysis of wild type and transgenic larvae exposed to MPP+, 3418 proteins were identified, in which 366 proteins were differentially regulated. In particular, we identified enzymes belonging to primary metabolism to be among proteins affected by MPP+ in wild type animals, but not affected in the transgenic line. Moreover, by performing protein profiling on isolated astrocytes we showed that an increase in astrocytic DJ-1 expression up-regulated a large group of proteins associated with redox regulation, inflammation and mitochondrial respiration. The majority of these proteins have also been shown to be regulated by Nrf2. These findings provide a mechanistic insight into the protective role of astroglial up-regulation of DJ-1 and show that our transgenic zebrafish line with astrocytic DJ-1 over-expression can serve as a useful animal model to understand astrocyte-regulated neuroprotection associated with oxidative stress-related neurodegenerative disease.

The non-protein amino acid β-methylamino-L-alanine (BMAA) is a neurotoxin present in microalgae and shown to accumulate in the food web. BMAA has been linked to the complex neurodegenerative disorder of Guam and to increased incidents sporadic ALS. Two main neurotoxic routes are suggested; an excitotoxic by acting as an agonist towards glutamate receptors and a metabolic by misincorporating into cellular proteins. We have used zebrafish, an increasingly used model for neurodegenerative diseases, to further identify signaling components involved in BMAA-induced toxicity. Zebrafish embryos were exposed to sub-lethal dosages of BMAA and a label-free proteomics analysis was conducted on larvae 4 days post fertilization. The exposed larvae showed no developmental abnormalities, but a reduced heart rate and increased expression of GSK3 isoforms. Search towards a reviewed database containing 2968 entries identified 480 proteins. Only 17 of these were regulated 2-fold or more in the exposed larvae. Seven of these proteins could be associated to glutamate receptor signaling and recycling. The remaining nine have all been linked to disturbance in protein homeostasis, reactive oxygen species (ROS) development or neuronal cell death. We also found that BMAA influenced the endocannabinoid system by up-regulation of fatty acid amide hydrolase (FAAH) and that FAAH inhibitor URB597 reduced the BMAA effect on heart rate and GSK3 expression.

Microplastics (MPs) are physical anthropogenic pollutants and their ability to act as contaminant vectors in biological matrices is of serious ecosystem and human health concern. In the present study, we have, for the first time, screened and detected MPs in the stomach of a select group of commonly consumed fish species from a municipal water supply lake (Eleyele) in Nigeria. A total of 109 fish samples consisting of eight (8) species: Coptodon zillii

The dopaminergic effect of PAH and PFAS mixtures, prepared based on environmental levels has been studied in juvenile female Atlantic cod (Gadus morhua). Benzo[a]pyrene, dibenzothiophene, fluorene, naphthalene, phenanthrene and pyrene were used to prepare a PAH mixture, while PFNA, PFOA, PFOS and PFTrA were used to prepare PFAS mixture. Cod were injected intraperitoneally twice, with either a low (1x) or high dose (20x) of each compound mixture or various combinations. After two week of exposure, levels of plasma 17β-estradiol (E2) were significantly high in high PAH/high PFAS treated groups. Dopamine: metabolite ratios (DOPAC/dopamine and HVA+DOPAC/dopamine) in brain homogenate changes with the levels of E2 in plasma except for high PAH/low PFAS and low PAH/high PFAS treated groups. In general, th mRNA levels inversely correlated with dopamine: metabolite ratios and gnrh2 mRNA levels. Respective decreases and increases of dr1 and dr2a after exposure to the high PAH dose were observed. Whereas, high PFAS exposure decreased both drs, leading to high plasma E2 concentrations. Other investigated endpoints suggest that these compounds at different doses and combinations have different toxicity threshold and mode of actions. These effects indicate potential alternations in feedback signalling processes within dopaminergic pathway by these contaminants.