APOEε4 increases trauma induced early apoptosis via reducing delayed rectifier K+ currents in neuronal/glial co-cultures model

Traumatic brain injury (TB!) is a commonly encountered emergency and severe neurosurgical injury. Previous studies have shown that the presence of the apolipoprotein E (APOE) epsilon 4 allele has adverse outcomes across the spectrum of TBI severity. Our objective was to evaluate the effects of APOE alleles on trauma induced early apoptosis via modification of delayed rectifier K+ current (I-k(DR)) in neuronallglial co-cultures model. An ex vivo neuronallglial co-cultures model carrying individual APOE alleles (epsilon 2, epsilon 3, epsilon 4) of mechanical injury was developed. Flow cytometry and patch clamp recording were performed to analyze the correlations among APOE genotypes, early apoptosis and I-k(DR). We found that APOE epsilon 4 increased early apoptosis at 24 h (p < 0.05) compared to the ones transfected with APOE epsilon 3 and APOE epsilon 2. Noticeably, APOE epsilon 4 significantly reduced the amplitude of the I-k(DR) at 24 h compared to the APOE epsilon 3 and APOE epsilon 2 (p < 0.05) which exacerbate Ca2+ influx. This indicates a possible effect of APOE epsilon 4 on early apoptosis via inhibiting I-k(DR) following injury which may adversely affect the outcome of TBI. (C) 2015 Elsevier Inc. All rights reserved.