Expression of Apolipoproteins D and E in Neurotoxicity Mediated by Glutamate

A marked increase in apolipoprotein D immunoreactivity is observed in hippocampus following neurotoxicity induced by KA (Table 6.3) (Ong et al., 1997). This increase in apolipoprotein D immunoreactivity occurs on the first day after KA injection, mainly in the cell bodies and dendrites of neurons (Fig. 6.3 A, 3B). Unlike the gray matter, no increase is observed in white matter tracts (Ong et al., 1997a). The significance of this upiegulation of apolipoprotein D remains unknown. However, apolipoprotein D binds to arachidonic acid (Morais Cabral et al., 1995), which is released by PLA2 stimulation. This could be a protective mechanism to limit the oxidative products from arachidonic acid, e.g. 4-HNE, after kainate injection. 

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). 

NF-icB, Nuclear factor-kappaB GFAP, glial fibrillary acidic protein /3-APP, /3-amyloid precursor protein TGF-/33, transforming growth factor-/33 Cdk4, cyclin-dependent kinase and p53, a tumor-suppressor gene. 

6 Glutamate Receptors and Other Neurochemical Parameters in Excitotoxicity 

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