Spatial cognitive deficits in an animal model of Wernicke-Korsakoff syndrome are related to changes in thalamic VDAC protein concentrations

- TD affects spatial learning and increased and decreased thalamic protein levels.
- Four thalamic protein changes are related to spatial cognitive performance of rats.
- Changes in VDAC, one of the four proteins, relate to rats' spatial learning.
- The association of VDAC is evident in the session with the worst performance.

Proteomic profiles of the thalamus and the correlation between the rats' performance on a spatial learning task and differential protein expression were assessed in the thiamine deficiency (TD) rat model of Wernicke-Korsakoff syndrome. Two-dimensional gel-electrophoresis detected 320 spots and a significant increase or decrease in seven proteins. Four proteins were correlated to rat behavioral performance in the Morris Water Maze. One of the four proteins was identified by mass spectrometry as Voltage-Dependent Anion Channels (VDACs). The association of VDAC is evident in trials in which the rats' performance was worst, in which the VDAC protein was reduced, as confirmed by Western blot. No difference was observed on the mRNA of Vdac genes, indicating that the decreased VDAC expression may be related to a post-transcriptional process. The results show that TD neurodegeneration involves changes in thalamic proteins and suggest that VDAC protein activity might play an important role in an initial stage of the spatial learning process.