The effect of apolipoprotein E4 on synchronous neural interactions in brain cultures
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In a previous study, we assessed the synchronous neural interactions (SNI) in a developing neural network in brain cultures on multielectrode arrays (Christopoulos et al. in J Neural Eng 9:046008, 2012). Here, we report on the effects of apolipoprotein E4 (apoE4) on these neural interactions. We carried out six experiments (five using rodent brain cultures and one using neuroblastoma cultures) in which we recorded local field potentials (LFP) from 59 sites for several days in vitro under the following conditions. In one experiment, we added to the culture media triglyceride (TG)-rich lipoproteins from a human subject with the apoE4/4 genotype, whereas in the other experiments, we added recombinant human apoE4. We found that SNI in the apoE4-treated cultures had higher coefficient of SNI variation, as compared to control cultures. These findings further document the role of SNI as a fundamental aspect of the dynamic organization of neural networks (Langheim et al. in Proc Natl Acad Sci USA 103:455–459, 2006. doi: 10.1073/pnas.0509623102; Georgopoulos et al. in J Neural Eng 4:349–355, 2007) and extend the effect of apoE4 on SNI (Leuthold et al. in Exp Brain Res 226:525–536, 2013) across different brain species (human, rodents), apoE source (TG-rich lipoproteins, recombinant), neural signals (MEG, LFP), and brain network (intact brain, developing brain in vitro). To our knowledge, this is the first study of the effects of apoE4 on neural network function in vitro.
KeywordsApolipoprotein E4 Brain culture Synchronous neural interactions Local field potentials
We thank Dean Evans and Dale Boeff for their valuable assistance with the cultures and recordings, and Laura Kalipe for her assistance with preparing the human apoE4/4 solution. This work was supported by the American Legion Brain Sciences Chair, the University of Minnesota, and the US Department of Veterans Affairs.
Conflict of interest
The authors declare that they have no conflicts of interest.
The study protocol was approved by the appropriate institutional review board and was performed in accordance with the ethical standards outlined in the Declaration of Helsinki.
The human participant provided written informed consent prior to participating in the study.
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