Isoform‐ and subcellular fraction‐specific differences in hippocampal 14‐3‐3 levels following experimentally evoked seizures and in human temporal lobe epilepsy

Abstract 14‐3‐3 proteins are a family of signaling molecules involved in diverse cellular functions, which can mediate anti‐apoptotic effects. Seizure‐induced neuronal death may involve programmed (apoptotic) cell death pathways and is associated with a decline in brain 14‐3‐3 levels. Presently, we investigated the subcellular localization and effects of seizures on isoforms of 14‐3‐3 in rat hippocampus, and contrasted these to findings in human temporal lobe epilepsy (TLE). All brain isoforms of 14‐3‐3 were detected in the cytoplasmic compartment of rat hippocampus, while 14‐3‐3γ and ‐ζ were also present in mitochondrial and microsome‐enriched fractions. Focally evoked seizures in rats significantly reduced 14‐3‐3γ levels within the microsome‐enriched compartment at 4 h, with similar responses for 14‐3‐3ζ, while cytoplasm‐localized 14‐3‐3β, ‐ε and ‐η remained unchanged. Analysis of human autopsy control hippocampus revealed similar 14‐3‐3 isoform expression profiles. In TLE samples, the microsome‐enriched fraction also showed differences, but here 14‐3‐3ε and ‐ζ levels were higher than controls. TLE sample 14‐3‐3 isoform abundance within the cytoplasmic fraction was not different to controls. This study defines the subcellular localization of 14‐3‐3 isoforms in rat and human hippocampus and identifies the microsome‐enriched fraction as the main site of altered 14‐3‐3 levels in response to acute prolonged and chronic recurrent seizures.