Astrocytes membranes

In addition to the permeability barrier of the capillary endothelium, highly active enzymes present in the brain endothelial cells, pericytes and astrocytes, represent a further metabolic component of the BBB that also restricts the entry of substances to the brain. This is further compounded by the presence of the p-glycoprotein active efflux system in the astrocyte membranes (see below) these various components work in parallel with the permeability barrier of the capillary endothelium, to form a multicomponent BBB. 

Recent studies have shown that p-glycoprotein is located in the astrocyte membranes (and not in the brain capillary endothelium as previously accepted) and that it functions by reducing the volume of distribution of the drug in the brain. Thus this efflux system, by restricting the transcellular flux of some molecules, may serve as a further barrier to drag delivery to the CNS. 

Vaalavirta L, Tahti H. 1995. Effects of selected organic solvents on the astrocyte membrane atpase in vitro. Clin Exp Pharmacol Physiol 22(4) 293-294. 

Water moving from the blood into the brain through an intact BBB has to cross three membranes luminal and abluminal endothelial cell membranes, and the membrane of the astrocyte foot processes (Kimelberg, 2004 Tait et al., 2008). High density of AQP4 is present in the vascular-facing astrocytic membranes. Although... 

In a recent review numerous examples were given of membrane ultrastructural textures consistent with the conformation discussed here [64]. Another obvious case of a conformation will be mentioned. The brain astrocytes are rich in potassium channels, which appear to play an important role in the regulation of the ion concentrations in the brain. Freeze-fracture electron micrographs of the outer astrocyte membrane contain patches of a periodic structure [65]. These ordered assemblies are thought to be potassium channels. In our membrane description these channels serve to plug the "holes" of a C D bilayer, whereas the rest of the membrane is in the conformation. 

Using all of the techniques outlined above, as well as radioautography, we have demonstrated a special type of junctional complex between neurites and astrocytic membranes in culture (Fig. 8), but the functional significance of this type of junctional complex is not clear at this time. However, repeated observations of the intimate association between neurons and astrocytes both in vivo and in vitro, coupled with the known beneficial effects of astrocytes upon the survival of immature neurons in cul-... 

Fig. 8. Electron micrograpn aemonstrating the formation of intermembranous electron dense junctions (thick arrows) between neuronal processes (NP) and astrocytic membrane. GF glial filaments.

Damage occurred most rapidly and most severely to thin neurites and neuronal cell bodies, while damage to astrocytes developed somewhat later, although both types of cells were irreversibly affected after 10 min in 0.2 mM or 20 min in 0.1 mM MMC. Following exposure to much lower concentrations (e.g., 0.01 mM) of MMC for 30-40 min, the progression of damage to the astrocytic membrane could be halted by placing the cells in normal culture media, after which a slow recovery to normal was observed. 

FIGURE 3.7 Cholesterol flux between astrocytes and neurons. Because cholesterol cannot travel as a free solute between the astrocyte and the neuron, it is incorporated in apoE-contairang lipoproteins (inset). The journey begins in the endoplasmic reticulum of astrocytes, where cholesterol is incorporated in lipoproteins. These lipoproteins are exported via ABC transporters. In neurons, cholesterol-enriched lipoproteins are taken up by lipoprotein receptors (LRPl). Note that the astrocyte has also to fulfill its own cholesterol needs, thus a part of neosynthesized cholesterol is incorporated in astrocytic membranes. 

Because of their strategic localization, astrocytes play a crucial role in maintaining the extracellular ionic homeostasis, provide energetic metabolites to neurons and remove excess of neurotransmitter in schedule with synaptic activity. In addition, the strategic location of astrocytes allows them to carefully monitor and control the level of synaptic activity. Indeed, number of papers during the last 15 years have shown that cultured astrocytes can respond to a variety of neurotransmitters with a variety of different patterns of intracellular calcium increases (Verkhratsky et al. 1998). Later on, studies performed in intact tissue preparations (acute brain slices) further established that the plasma membrane receptors can sense external inputs (such as the spillover of neurotransmitters during intense synaptic activity) and transduce them as intracellular calcium elevations, mostly via release of calcium from internal stores (Dani et al. 1992 Murphy et al. 1993 Porter and McCarthy... 

Winship IR, Plaa N, Murphy TH (2007) Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J Neurosci 27 6268-6272 Wu MM, Buchanan J, Luik RM, Lewis RS (2006) Ca store depletion causes STIMl to accumulate in ER regions closely associated with the plasma membrane. J Cell Biol 174 803-813 Wyss-Coray T (2006) Inflammation in Alzheimer disease driving force, bystander or beneficial response Nat Med 12 1005-1015... 

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