Hippocampal synapsin isoform levels are linked to spatial memory enhancement by SGS742

Synapsins are essential proteins for synaptic plasticity and there is no information available for their role in cognitive enhancement (CE) of spatial memory formation. It was therefore the aim of the study to link individual synapsin proteins and their isoforms to spatial memory formation enhanced by SGS742 in the mouse. Extracted hippocampal proteins from a cognitive study treating OF1 mice with the cognitive enhancer SGS742 and tested in the Morris water maze, were run on two-dimensional gel electrophoresis. Subsequently, protein spots were unambiguously identified by qQ-TOF mass spectrometry. Quantification of proteins from four groups (NaCl-treated mice, SGS742-treated mice, SGS742-treated yoked controls, and NaCl-treated yoked controls) was carried out according to an in-gel stable isotope labeling method. A total of 17 protein spots representing synapsin isoforms were identified and quantified. Using quantification of individual synapsin isoforms showed that these can be clearly assigned to CE by the GABAB antagonist SGS742. Quantitative determination of individual synapsin isoform showed an increase in SGS742-treated mice (mean+/-SD) of ratios between light and heavy stable isotope labeled synapsin protein (SGS742 vs. controls: 2.19+/-0.41 for synapsin Ia, and 1.41+/-0.81 for synapsin IIa). Synapsins Ib and IIb were not linked to CE. The NaCl-treated controls and the use of yoked controls that were ruling out swimming- and stress-mediated changes of synapsins, unequivocally allow to propose a role for synapsins Ia and IIa in the mechanism of CE of spatial memory formation.