The potential of apolipoprotein E4 to act as a substrate for primary cultures of hippocampal neurons

Abstract The E4 isoform of apolipoprotein (apoE4) is known to be a major risk factor for Alzheimer's Disease (AD). Previous in vitro studies have shown apoE4 to have a negative effect on neuronal outgrowth when incubated with lipids. The effect of apoE4 itself on the development of neurons from...

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Published in:	Biomaterials Vol. 34; no. 11; pp. 2694 - 2700
Main Authors:	Kim, Kwang-Min, Vicenty, Janice, Palmore, G. Tayhas R
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-04-2013
Subjects:	Advanced Basic Science Alzheimer Disease - metabolism Alzheimer Disease - physiopathology Animals Apolipoprotein E4 Apolipoprotein E4 - metabolism Cell Adhesion Cells, Cultured Central nervous system (CNS) Dentistry Heparan Sulfate Proteoglycans - metabolism Hippocampal neuron Hippocampus - cytology Hippocampus - metabolism Laminin Laminin - metabolism Neuronal culture substrates Neurons - cytology Neurons - metabolism Primary Cell Culture - methods Rats Risk Factors Tissue engineering Up-Regulation Apolipoprotein E4 Laminin Hippocampal neuron Neuronal culture substrates Tissue engineering Central nervous system (CNS)
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Summary:	Abstract The E4 isoform of apolipoprotein (apoE4) is known to be a major risk factor for Alzheimer's Disease (AD). Previous in vitro studies have shown apoE4 to have a negative effect on neuronal outgrowth when incubated with lipids. The effect of apoE4 itself on the development of neurons from the central nervous system (CNS), however, has not been well characterized. Consequently, apoE4 alone has not been pursued as a substrate for neuronal cultures. In this study, the effect of surface-bound apoE4 on developmental features of rat hippocampal neurons was examined. We show that apoE4 substrates elicit significantly enhanced values in all developmental features at day 2 of culture when compared to laminin (LN) substrates, which is the current substrate-of-choice for neuronal cultures. Interestingly, the adhesion of hippocampal neurons was found to be significantly lower on LN substrates than on glass substrates, but the axon lengths on both substrates were similar. In addition, this study demonstrates that the adhesion- and growth-enhancing effects of apoE4 substrates are not mediated by heparan sulfate proteoglycans (HSPGs), proteins that have been indicated to function as receptors or co-receptors for apoE4. In the absence of lipids, apoE4 appears to use an unknown pathway for up-regulating neuronal adhesion and neurite outgrowth. Our results indicate that apoE4 is better than LN as a substrate for primary cultures of CNS neurons and should be considered in the design of tissue engineered CNS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2013.01.012