Proteomic analysis of time-dependent changes in proteins expressed in mouse hippocampus during synaptic plasticity induced by GABAA receptor blockade

Protein synthesis is required for long-lasting synaptic plasticity. We examined the time-dependent changes in protein expression that occurred in the hippocampus during synaptic plasticity using two-dimensional gel electrophoresis followed by mass spectrometry. The levels of 15 proteins were significantly changed in mouse hippocampus 8 h after bicuculline application (1.0 mg/kg, i.p.). Expression of 14 proteins (i.e., dihydropyrimidinase-related protein 2, α-tubulin isotype M-α-2, tubulin β-1 chain, tubulin β-2A chain, protein disulfide-isomerase ERp61 precursor, chaperonin-containing T complex polypeptide 1 β subunit, T complex polypeptide 1 [partial], creatine kinase B-type, cytosolic malate dehydrogenase [partial], vacuolar adenosine triphosphatase subunit A, and uncharacterized protein LOC433182) was increased and expression of one protein (i.e., actin γ, cytoplasmic 1) was decreased. Western blotting also validated the changes in dihydropyrimidinase-related protein 2, creatine kinase B-type, and vacuolar adenosine triphosphatase subunit A levels in mouse hippocampus 8 h after bicuculline application. The identified proteins were effectors of cellular functions including neuronal differentiation, cytoskeletal dynamics, folding of proteins, stress response, energy metabolism, synapse formation, and unknown function. Taken together, these findings indicate that the identified proteins play an important role in synaptic plasticity in the hippocampus.