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Polystyrene nanoplastics are one of the most pervasive environmental contaminants and have been shown to infiltrate multiple organ systems following ingestion. Studies in several animal models and humans have demonstrated that nanoplastics can cross the blood-brain barrier. Additionally, there is evidence that plastics will induce an inflammatory response in the brain involving reactive gliosis of microglia and astrocytes. This process has yet to be thoroughly investigated in the zebrafish model system in the context of micro-/nanoplastic ingestion. In the current study, we examined microglial and astrocytic phenotypes in the adult zebrafish telencephalon after consuming food contaminated with 44 nm polystyrene spheres for 14 and 28 days. The data indicate that neuroinflammation was elevated. Specifically, increased levels of activated microglia were observed via western blot and confocal microscopy following 14 days of polystyrene ingestion, and reactive astroglia were elevated after 28 days of polystyrene ingestion but not after 14 days. Evidence from this study supports the notion that consuming nanoplastic-contaminated food will induce reactive gliosis in the adult zebrafish telencephalon.

Here is evaluated a strategy for stem cell repair of nervous tissue with a potential therapeutic application of a transdermal microneedle stromal-derived-factor 1 (SDF-1) chemokine delivery system. The central question of this research focuses on whether enhanced SDF-1 signaling to mesenchymal stem cells (MSCs) at injury sites promotes more effective regeneration of damaged nerves. SDF-1/CXCL12 is a potent chemokine protein known to bind to ligands CXCR4 and CXCR7, both of which are proven to drive processes involved with nervous tissue regeneration (Carbajal 2010). While it is shown that SDF-1 delivery systems can facilitate repair of nerves, many of the mechanisms behind this are still unclear (Purcell 2012). In all studies evaluated in this work, significant neuro-regenerative improvements were seen as: improved MSC chemotaxis, greater volumes of repairing cells at injury sites, and an improved quality of injury repair. Many factors and cell types are also involved in nerve repair and each injury involves a coordination of signaling and checkpoints (Jiang 2017, Sullivan 2016). This study looks closely at specific nervous tissue damage and repair systems, finding that, in all cases, SDF-1 supplementation improves neural regeneration. This study concludes that further investigation of timed-release SDF-1 in microspheres via microneedle patch, using the tested approaches described here, is warranted to understand diffusion rates, cell signaling, inflammation response, fibrosis, and bio-compatibility of such a repair system.

The assembly of the β-amyloid peptide (Aβ) into amyloid fibrils is essential to the pathogenesis of Alzheimer's disease. This work demonstrates the novel application of photoaffinity crosslinking to determine high-resolution structural constraints on Aβ monomers within amyloid fibrils. Photoreactive Aβ 1-40 ligands were synthesized by substituting L-p-benzoyl-phenylalanine (Bpa) for phenylalanine at position 4 (Aβ 1-40 F4Bpa), phenylalanine at position 19 (Aβ 1-40 F19Bpa), or tyrosine at position 10 (Aβ 1-40 Y10Bpa). These peptides were incorporated into synthetic amyloid fibrils, and upon photoactivation produced crosslinked Aandβ dimers. The position of photoinsertion was analyzed by proteolysis of Aβ dimers dissociated from the fibrils, followed by mass spectrometric analysis. MALDI-TOF mass spectrometry identified a crosslinked tryptic fragment formed by the photoinsertion of Bpa4 into the C-terminal region of Aβ 1-40 . MS/MS experiments and further chemical modifications of the crosslinked dimer led to the localization of the intermolecular photocrosslink between the ketone of the Bpa4 side chain and the β-methyl group of the Met35 side chain. Aβ fibrils containing Bpa19-Aβ formed covalent crosslinked dimers, however the position of the crosslink could not be determined. Trypsin digestion of Bpa10-Aβ crosslinked dimers generated a crosslinked fragment in which Bpa10 photoinserts into the Aβ29-40 region of Aβ 1-40 . This finding is consistent with the intermolecular constraint produced by the Bpa4 photocrosslinking studies. Taken together these studies provide strong support for an antiparallel alignment of Aβ molecules as they assemble into amyloid fibrils. Reactive gliosis is an invariant feature of the central nervous system's response to injury. The hypertrophic astrocytes that form the gliotic scar influence the fate of surviving neurons through both physical and chemical interactions. To elucidate the molecular mediators of reactive gliosis, a proteomic analysis of endothelin-1 stimulated hypertrophy of cultured astrocytes was performed. Specific mediators of cytoskeletal reorganization (caldesmon, calponin, alpha B-crystallin, stathmin, CRMP-2), cell adhesion (vinculin, galectin-1), and signal transduction (RACK-1) were among the proteins differentially expressed by ET-1 treated astrocytes. The results validate the use of proteomic arrays to quantitate differential protein expression levels on a more global scale and presents potential molecular mechanisms that drive reactive hypertrophy and modulate the astrocytes' interactions with neurons following CNS injury.