Neurotoxic mediators

D Apuzzo M, Relink A, Loetscher M, Hoxie JA, Clark-Lewis I, Melchers F, Baggiolini M, Moser B (1997) The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol 27 1788-1793 Dawson VL, Dawson TM, Uhl GR, Snyder SH (1993) Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc Natl Acad Sci USA 90 3256-3259... 

Increase of free cytosolic calcium is toxic for various reasons. Among them are the diminution of ATP levels (Tsuji et al. 1994), the protease and lipase activation, and the FR production that causes a peroxidation of lipids. The inflow of calcium in the terminals could also increase the release of endogenous excitatory amino acids and propagate neuronal damage through positive feedback (Choi and Hartley 1993). Glutamic neurotoxicity mediated by calcium follows three stages ... 

Ornithine Decarboxylase and Polyamines in Neurotoxicity Mediated by Glutamate... 

Similarly, apolipoprotein E expression increases in neurotoxicity mediated by KA (Table 6.3) (Boschert et al., 1999). Apolipoprotein E is a major lipoprotein in the brain. It is involved in the transport, distribution, and other aspects of cholesterol homeostasis. Apolipoprotein E also plays a dominant role in the mobilization and redistribution of brain lipids in repair, growth, and maintenance of nerve cells (Mahley, 1988). The secretion of apolipoproteins E and D may be differentially regulated in cultured astrocytes. In cell culture systems this depends upon the extracellular lipid milieu (Patel et al., 1995). During neurotoxicity mediated by KA, apolipoprotein E levels increase moderately in astrocytes and apolipoprotein E mRNA increases very strongly in clusters of CA1 and CA3 pyramidal neurons. Based on hybridization in situ and immunohistochemical studies, expression of apolipoprotein E in neurons may be a part of a rescue program to counteract neurodegeneration mediated by KA (Boschert et al., 1999). 

Table 6.3 Other neurochemical parameters associated with neurotoxicity mediated by glutamate and its analogs...

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