Human apolipoprotein E isoform-specific differences in neuronal sprouting in organotypic hippocampal culture.
The apolipoprotein E (ApoE) epsilon4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease. A role for ApoE is implicated in regeneration of synaptic circuitry after neural injury. In the in vitro mouse organotypic hippocampal slice culture system, we previously showed that cultures derived from ApoE-knockout mice are defective in mossy fiber sprouting into the dentate gyrus molecular layer. This sprouting defect was rescued in cultures from transgenic mice expressing ApoE3 under the control of the human promoter and in ApoE-knockout cultures treated with ApoE3-conditioned media. Although the ApoE3 transgene fully restored sprouting, ApoE4 restored sprouting to only 58% of ApoE3 levels. These data indicate that ApoE isoform-specific effects on neuroregeneration may contribute to its genetic risk for Alzheimer's disease.
Teter
B
B
Veterans Administration Medical Center, Sepulveda, California 91343, USA.
Xu
P T
PT
Gilbert
J R
JR
Roses
A D
AD
Galasko
D
D
Cole
G M
GM
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017077:Culture Media, Conditioned; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism* / Q000648:ultrastructure; D009410:Nerve Degeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins