Brain area- and isoform-specific inhibition of synaptic plasticity by apoE4.
The allele E4 of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor of Alzheimer's disease (AD), inhibits the improvements in learning and memory which result from exposure of apoE transgenic mice to environmental stimulation (ES). In the present study, we investigated the extent to which these cognitive deficits are associated with distinct presynaptic, postsynaptic and axonal impairments and whether these effects are brain area-specific. Exposure to an enriched environment of young mice transgenic for human apoE3, which is the AD benign apoE allele, increased the levels of the presynaptic protein synaptophysin and of the dendritic marker MAP-2 in the hippocampus and entorhinal cortex, whereas the corresponding levels of these proteins in the apoE4 transgenic mice were unaffected by the enriched environment. In contrast, the levels of synaptophysin and MAP-2 in the motor cortex were elevated by environmental stimulation in both the apoE3 and the apoE4 transgenic mice. These findings show that apoE4 inhibits synaptic plasticity following environmental stimulation and that this effect is both isoform- and brain area-specific.
Levi
Ofir
O
The Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
Jongen-Relo
Ana L
AL
Feldon
Joram
J
Michaelson
Daniel M
DM
D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology*; D001369:Axons / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D019922:GAP-43 Protein; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; D017661:Receptors, Presynaptic; D016708:Synaptophysin