The Membrane And Its Effects On Human Development - 860 Words

It is generally accepted that resting CaMKIIÃŽ ² bundles and stabilizes actin cytoskeleton. Transient activation of CaMKIIÃŽ ² relaxes cytoskeleton, promotes actin polymerization and CaMKIIÃŽ ² recruitment, and favors cytoskeleton growth. This model has been shown in both synaptogenesis (Okamoto et al., 2007) and OL maturation (Waggener et al., 2013). Based on this theory, we proposed that prolonged CaMKIIÃŽ ² activation by NMDA-R-mediated Ca2+ influx leads to destabilization of actin cytoskeleton and membrane disintegration in mature OLs. Although our experiments unambiguously showed that NMDA-R activation results in CaMKIIÃŽ ² activation, direct proof that links CaMKIIÃŽ ² activation and membrane reduction are lacking. All the existing CaMKIIÃŽ ² inhibitors†¦show more content†¦As mentioned in chapter 5, a repeated measure experiment using OLs from CaMKIIÃŽ ²A303R mice will be the best way to investigate this question. The CaMKIIÃŽ ²A303R mutant retains its ability to bund le F-actin, but loses its Ca2+/CaM binding capacity. Based on our proposed model, Tat-induced [Ca2+]i increase should have no effect on OL membrane area since Ca2+/CaM can not bind and activate CaMKIIÃŽ ²A303R, and promotes its release from actin cytoskeleton. Most of our experiments are done in mice cells. Since HIV is a human disease, we used an hBrnAgg model to try to verify our finding in human cells. We thought that the hBrnAgg model serves our experiments best because 1) it mimics the in vivo environment with the presence of all major CNS cell types, 2) myelination has been observed in the model by other investigators, thus fulfill the needs of studying effect of HIV/Tat on both OLs and myelin, and 3) the hBrnAgg model can be maintained for a long period of time (up to 60 days), made it a good model to study long-term effect of HIV/Tat. Our immunostaining experiments suggested that there are far less OLs in the aggregates than we expected. Under EM, plenty of synaptic structures, both symmetric and asymmetric, were observed in the hBrnAgg. However, cells with typical mature OL characteristics, including dark cytoplasm and nucleus, elongated, thin strands of endoplasmic reticulum; numerous mitochondria, and stacks of Golgi apparatus, were rarely