Differential neurotrophic effects of apolipoprotein E in aged transgenic mice.
The present study seeked to determine whether the neurodegenerative and cognitive alterations in aged apolipoprotein E-deficient mice are differentially reversed by transgenic overexpression of human apolipoprotein-E3 vs. apolipoprotein-E4 in the background of deficient endogenous apolipoprotein E. These studies showed dendritic alterations in pyramidal neurons of apolipoprotein-E4 transgenic mice, similar to the ones observed in apolipoprotein E-deficient mice. However, these mice had a preserved density of synaptophysin-immunoreactive presynaptic terminals. In contrast, mice overexpressing apolipoprotein-E3 showed no synapto-dendritic alterations. Analysis of behavioral performance in the Morris water maze showed that while apolipoprotein E-deficient mice performed poorly, overexpression of apolipoprotein-E3 and, to a lower extent apolipoprotein-E4, resulted in an improved performance. This study supports the contention that, compared with apolipoprotein-E4, apolipoprotein-E3 might have a greater neurotrophic in vivo effect in aged mice.
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D003712:Dendrites / Q000737:chemistry / Q000502:physiology; D005625:Frontal Lobe / Q000737:chemistry / Q000502:physiology; D019922:GAP-43 Protein / Q000032:analysis; D006801:Humans; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology; D013569:Synapses / Q000737:chemistry / Q000502:physiology