Phosphoproteomic and proteomic analysis of early epileptogenesis in mice at 4 and 24 h post-status epilepticus

The phosphorylation-based signalling and protein changes occurring in the early phases after a pathophysiological insult, like status epilepticus, have not been detailed. To this end, the hippocampi of mice treated with pilocarpine and diazepam were examined by mass spectrometry at 4 and 24 h post-status epilepticus at vast depth using the tandem mass tag 11-plex system. In the accompanying article, the results implicated posttranscriptional regulatory proteins as early targets of increased phosphorylation. Also, the major targets of decreased phosphorylation at 4 h and 24 h were a subset of post synaptic density scaffold proteins, ion channels and neurotransmitter receptors. Many proteins targeted by dephosphorylation at 4 h also had decreased protein abundance at 24 h, indicating a phosphatase-mediated weakening of synapses.