Cholesterol and Monocyte Differentiation

Topics of research today included prion-induced disruption of cholesterol homeostasis and monocyte differentiation after crossing the blood brain barrier into the CNS. The subjects are relatively unrelated, but nonetheless interesting. Through some unclear mechanism once monocytes reach areas of inflammation in the brain, certain molecules like TGF[beta] ligands induce the signalling pathway that ultimately produces a microglial-like phenotype. Through a SMAP2/3 pathway, microglial markers CX3CR1 and Ilba-1 are upregulated and DC markers CD11c, CD86, and MHC II are downregulated. This emphasizes the importance of TGF[beta] in inflammatory response.

[Read more…]

New Significance for ATP

ATP is released from damage neurons are is usually grouped with other pro-inflammatory signals to microglia or DAMPS, which usually act through  a TLF4/MyD88 pathway. But ATP can be more effective than others in activating, either by triggering assembly of increasing expression of pro-caspase-1, NLRP inflammasomes. Microglia and astrocytes have unique inflammasomes that can produce much of the same cytokines, including IL-1[beta]. NLRP3 (in  microglia) and NLRP2 in astrocytes may differentiate over time the quantity of cytokines release based on the disease pathogenesis.

[Read more…]

Week VI

I spent a great deal of time this week finalizing my prion proliferation model and Thursday I made all the connection clearer. The model is compartmentalized into CNS, PNS, spleen, and lymph node. I actuality activated T-cells should enter the lymph node through the blood stream and t then move onto the PNS, but I didn’t account for this in my set-up so the concept is not demonstrated. The blood vessel is an important component I wish to include, but now that I have visualized my entire model the entire scope is alarming! Right now I have over 460 species, and at least 14 cells split into 5 sections. I have written out all of the necessary concepts like migration, replication, phagocytosis/caveosome formation, oxidative stress, cytokine release, and overproduction of DAMPs and under production of anti-inflammatory agents. I even made an illustration of my model on the white board. I will need to include cells outside of the CNS to demonstrate proliferation, but perhaps there is a more simplistic way to represent this.

[Read more…]

Organized Prion Proliferation

So I finally straightened out all of the lines in my prion proliferation model and it is massive! I have a total of 656 different species included and now four compartments: the CNS, PNS, spleen, and lymph node. I also show migratory paths and several instances of phagocytic activity withing the the CNS. There are still things to be worked out and added, like correct chemokine-receptor pairings and determination of preferential conditions.

[Read more…]

Nothing New To Report

photo (1)

[Read more…]