Neurobiology of disease
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Neurobiology of disease · Nov 2018
A differentiating neural stem cell-derived astrocytic population mitigates the inflammatory effects of TNF-α and IL-6 in an iPSC-based blood-brain barrier model.
Inflammation can be a risk factor for neurodegenerative diseases such as Alzheimer's disease (AD) and may also contribute to the progression of AD. Here, we sought to understand how inflammation affects the properties of the brain microvascular endothelial cells (BMECs) that compose the blood-brain barrier (BBB), which is impaired in AD. A fully human in vitro BBB model with brain microvascular endothelial cells derived from induced pluripotent stem cells and differentiating neural stem cell (NSC)-derived astrocytic cells was used to investigate the effects of neuroinflammation on barrier function. ⋯ Despite the presence of several pro-inflammatory cytokines, the NSC-derived astrocytic cells mitigated the effects of inflammation measured by a restoration of transendothelial electrical resistance and IgG permeability. These results also suggest a breakdown in transcellular transport that precedes any increase in paracellular permeability in neuroinflammation. This model has the potential to resolve questions about neurodegenerative disease progression and delivery of therapeutics to the brain.
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Neurobiology of disease · Nov 2018
Microstructural alterations of cortical and deep gray matter over a season of high school football revealed by diffusion kurtosis imaging.
To probe microstructural changes that are associated with subconcussive head impact exposure in deep and cortical gray matter of high school football players over a single season. ⋯ DKI may yield valuable biomarkers for evaluating the severity of brain injuries associated with subconcussive head impacts in contact sport athletes.
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Neurobiology of disease · Nov 2018
D159 and S167 are protective residues in the prion protein from dog and horse, two prion-resistant animals.
Prion diseases are fatal neurodegenerative diseases caused by misfolding of the prion protein (PrP). These conditions affect humans and animals, including endemic forms in sheep and deer. Bovine, rodents, and many zoo mammals also developed prion diseases during the "mad-cow" epidemic in the 1980's. ⋯ Replacing these key residues with the corresponding amino acids in hamster PrP showed that mutant horse (S167D) and dog (D159N) PrP are highly toxic, whereas mutant rabbit (S174 N) PrP is not. These results confirm the impact of S167 and D159 in local and long-range structural features in the globular domain of PrP that increase its stability, while suggesting the role of additional residues in the stability of rabbit PrP. Identifying these protective amino acids and the structural features that stabilize PrP can contribute to advance the field towards the development of therapies that halt or reverse the devastating effects of prion diseases.