Apolipoprotein E expression by neurons surviving excitotoxic stress

Abstract

In the adult brain, apolipoprotein E (apoE) mRNA is thought to be expressed by nonneuronal cells. Yet, when a brain damage has occurred, the protein is found in neurons. We have studied apoE expression following systemic kainic acid (KA), injected in rats to induce hippocampal neurodegeneration. We describe two effects. First, a moderate increase of apoE levels in astrocytes. Second, and unexpected, a very strong increase of apoE mRNA levels in clusters of CA1 and CA3 pyramidal neurons. Neuronal identity of these cells is supported by a series of observations. First, apoE hybridization signals were found in cells with morphological characteristics of pyramidal neurons. Second, the cells were positive for the neuronal marker MAP2. Third, the cells were negative for the astrocytic marker GFAP and for the microglia marker OX42. Fourth, the same distribution pattern was found with probes hybridizing to c-fos, a transcription factor transiently expressed in neurons under stress. At 48 and 72 h following KA, most of the excitotoxic cell death had already occurred. Since no morphological signs of programmed cell death were observed in apoE-positive pyramidal neurons, we suggest that expression of apoE by neurons may be part of a rescue program to counteract neurodegeneration.