Hydrocephalus induces dynamic spatiotemporal regulation of aquaporin-4 expression in the rat brain

<p>Abstract</p> <p>Background</p> <p>The water channel protein aquaporin-4 (AQP4) is reported to be of possible major importance for accessory cerebrospinal fluid (CSF) circulation pathways. We hypothesized that changes in AQP4 expression in specific brain regions correspond to the severity and duration of hydrocephalus.</p> <p>Methods</p> <p>Hydrocephalus was induced in adult rats (~8 weeks) by intracisternal kaolin injection and evaluated after two days, one week and two weeks. Using magnetic resonance imaging (MRI) we quantified lateral ventricular volume, water diffusion and blood-brain barrier properties in hydrocephalic and control animals. The brains were analysed for AQP4 density by western blotting and localisation by immunohistochemistry. Double fluorescence labelling was used to study cell specific origin of AQP4.</p> <p>Results</p> <p>Lateral ventricular volume was significantly increased over control at all time points after induction and the periventricular apparent diffusion coefficient (ADC) value significantly increased after one and two weeks of hydrocephalus. Relative AQP4 density was significantly decreased in both cortex and periventricular region after two days and normalized after one week. After two weeks, periventricular AQP4 expression was significantly increased. Relative periventricular AQP4 density was significantly correlated to lateral ventricular volume. AQP4 immunohistochemical analysis demonstrated the morphological expression pattern of AQP4 in hydrocephalus in astrocytes and ventricular ependyma. AQP4 co-localized with astrocytic glial fibrillary acidic protein (GFAP) in glia limitans. In vascular structures, AQP4 co-localized to astroglia but not to microglia or endothelial cells.</p> <p>Conclusions</p> <p>AQP4 levels are significantly altered in a time and region dependent manner in kaolin-induced hydrocephalus. The presented data suggest that AQP4 could play an important neurodefensive role, and may be a promising future pharmaceutical target in hydrocephalus and CSF disorders.</p

Publisher Correction: On the issue of transparency and reproducibility in nanomedicine

© 2019, Springer Nature Limited. In the version of this Correspondence originally published, Christine Dufès was incorrectly written as Christine Dufés. This has been corrected in the online versions of the Correspondence

On the issue of transparency and reproducibility in nanomedicine.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds

An assessment of the importance of exposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

According to the United Nations, plastic pollution in the natural environment has been identified as one of the biggest environmental challenges of this century and has become a cause for an emerging international concern. It has been predicted that up to 12 million tons of plastic waste reach the aquatic environment annually. Therein, UV-radiation induced photo-oxidation, mechanical weathering and biological degradation contribute to the fragmentation of plastic litter to the micro- or even nanoscale. Microplastics (MPs) thus have become prominent pollutants in the aquatic environment, and their prevalence has been documented in every aquatic ecosystem studied. MPs enter aquatic food webs, also reaching humans, the top consumers in the food chain. The omnipresence of small microscopic plastic particles in the aquatic environment presents several ecotoxicological concerns. Firstly, MP fragments can interact with aquatic organisms and act as physical or mechanical stressors. Secondly, MPs can be toxic, as some polymers consist of potentially hazardous monomers. Synthetic, petroleum-derived polymers can also contain functional additives, impurities or chemical residuals, which are not chemically bound to the polymeric material and thus have the potential to leach out and cause diverse toxicological effects. Lastly, plastic polymers are known to absorb persistent hydrophobic organic pollutants from the environment. MPs have been suggested to act as vectors of environmental contaminants into organisms, promote bioaccumulation of toxic compounds, and cause biological effects in aquatic biota. It remains widely debated whether MPs are important vectors of chemicals for aquatic animals, including fish, and whether MP ingestion by edible fish species can impact human food quality and safety. This PhD project addressed some of these prevailing concerns, and investigated biological fate and impacts of MPs and associated chemicals in fish. It has been shown that exposure route can play an important role in particle-organism interactions and can determine the organismal uptake and localization of plastic particles in fish [Paper I]. Plastic nanoparticles interact with aquatic organisms: they can enter fish via contaminated prey (trophic transfer) and they can be directly ingested and/or adhere to organismal surfaces. Ingested nanoplastics can accumulate in the gastrointestinal tract and can then be internalized by the intestinal cells. Plastic ingestion is regarded as an environmentally relevant particle pathway in fish, and it facilitates their entrance into aquatic food chains. Studies included in this thesis also explored biological effects derived from the ingestion of larger, micro-sized plastic particles, at sizes commonly extracted from biological and environmental matrices, and which entail environmentally relevant chemical exposures [Papers II-III]. Direct impacts resulting from MP ingestion were found to be negligible, as no adverse effects were observed on fish intestinal physiology. Indirect, chemical exposure related effects resulting from ingestion of contaminated MPs were also minor. No indications of hepatic stress (oxidative stress, detoxification, endocrine disruption) were observed. It was concluded that MPs did not act as mechanical and chemical hazards upon ingestion, and are unlikely to cause adverse effects on organismal health. Although MPs showed capacity to associate with environmental contaminants [Papers II-IV], the transfer of pollutants from particles into fish via ingestion, as well as accumulation and biological impacts were suspected to be low [Papers II-IV]. The early findings presented in this thesis suggest that ingestion of MPs by commercial fish species does not significantly diminish the oxidative stability of commercial fish products, and MP-mediated chemical exposure does not pose an evident concern for human food quality and product shelf-life

Determining ecotoxicity drivers and biodegradation kinetics of discharged chemicals in produced water from oil and gas extraction in the North Sea

Since the late 1990’s the “zero harmful discharge” regime related to offshore oil and gas extraction has been implemented on the Norwegian Continental Shelf. It has also gained traction in other areas of the North Sea due to OSPAR regulations. However, the holistic understanding of ecotoxicity drivers and biodegradation kinetics of this complex mixture is still lacking. The main goal of the MERIT project (Intelligent testing strategy for Minimizing EnviRonmental ImpacTs of produced water) was to develop a method for the quantitative estimation of drivers and the potential for reducing environmental impacts to acceptable levels. We summarize the findings of the project with focus on 1) identifying ecotoxicity drivers through whole effluent testing supported by toxicity identification evaluation and 2) determining environmentally relevant biodegradation kinetics of discharged chemicals in produced water. We present a testing strategy using empirical data and samples from five different platforms in the North Sea to align with the goals of minimizing environmental impacts of produced water