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P3–206: The effects of ApoE4 on brain inflammation following acute and chronic stimulation with LPS
Author(s) -
Ophir Gal,
Michaelson Daniel M.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1475
Subject(s) - inflammation , microglia , apolipoprotein e , stimulation , neurodegeneration , genetically modified mouse , endocrinology , medicine , transgene , pathogenesis , biology , immunology , disease , gene , biochemistry
and prevents the improvements in learning and memory which are induced by environmental stimulation. Objective(s): In the present study, we investigated the extent to which the cognitive and synaptic impairments of the apoE4 mice following environmental stimulation are related to the effects of apoE4 on either neuronal death or neuronal birth. Methods: This revealed that the level of neurogenesis in the hippocampal dentate gyrus (DG) subfield under regular conditions is elevated isoform specifically in the apoE4 transgenic mice. Furthermore, environmental stimulation, which elevated the levels of neurogenesis in the DG of apoE3 transgenic and wild type mice, had the opposite effect on the apoE4 mice, in which it triggered apoptosis and reduced neurogenesis. Analysis of the stages of the neurogenesis cascade which are affected by apoE revealed that the first lineage which is activated by apoE3 upon environmental stimulation, is progenitor cells which contain doublecortin and no nestin, and that the stimulation of neurogenesis by apoE4 under regular conditions is further upstream and is associated with activation of progenitor cells which contain both doublecortin and nestin. Conclusions: These animal model findings suggest that, whereas measures such as environmental enrichment which enhance neurogenesis may be beneficial to apoE3 positive patients, they could be harmful when applied to patients who carry apoE4. Conversely, antiapoptotic treatments may be more effective in apoE4 than in apoE3 patients.