Presence of apolipoprotein E immunoreactivity in degenerating neurones of mice is dependent on the severity of kainic acid-induced lesion

Apolipoprotein E (apoE) is a major apolipoprotein in the central nervous sy stem (CNS) that may play a role in various CNS disorders. ApoE is primarily localised in astrocytes, but neuronal apoE mRNA expression has been demons trated in normal and diseased human brain, as well as in ischaemic rat brai n. To obtain further insight into the role of apoE in neuronal degeneration in the CNS and conditions of neuronal apoE localisation, we have investiga ted in mice the distribution of apoE following neuronal injury induced by k ainic acid (n=35, 25 or 35 mg kainic acid/kg BW). Consecutive series of bra in sections were immunostained for apoE and markers for astroglia (GFAP) an d microglia/macrophage cells (CR3). Degenerating neurones were identified w ith a silver-degeneration staining technique. The intensity and cellular di stribution of apoE-immunoreactivity (apoE-ir) was dependent on the severity of neuronal injury. Mice that developed mild neuronal degeneration, restri cted to a subset of neurones in the hippocampus, showed increased apoE-ir i n astrocytes concomitant with increased GFAP-ir and mild microgliosis. In t hese mice, no neuronal apoe-ir was detected. In contrast, mice developing s evere neuronal injury in the hippocampus - frequently also showing degenera tion in other brain regions including cortex, thalamus, striatum and amygda la - showed intense apoE-ir in degenerating neurones. Surrounding the lesio n, apoE-ir was increased in neuropil recurrently whereas GFAP-ir astrocytes disappeared. Thus, in mice apoE accumulates in degenerating neurones in co nditions of severe neuronal injury putatively in association with disruptio n of the glial network. (C) 2000 Elsevier Science B.V. All rights reserved.