Proteomic analysis of rat prefrontal cortex after chronic valproate treatment

Abstract

Valproic acid (VPA) is commonly used to treat bipolar disorder (BD), but its therapeutic role has not been clearly elucidated. To gain insights into VPA's mechanism of action, proteomic analysis was used to identify differentially expressed proteins in the rat prefrontal cortex (PFC), a region particularly affected in BD, after 6 weeks of VPA treatment. Proteins from PFCs of control and VPA-treated rats were separated by 2D-DIGE and identified by mass spectrometry. Among the 2,826 protein spots resolved, the abundance of 19 proteins was found to be significantly altered in the VPA-treated group (with the levels of three proteins increasing and 16 decreasing). Seven proteins whose levels were significantly altered after chronic VPA exposure were quantified by Western blot analysis. The 19 identified proteins represent potential new targets for VPA action and should aid in our understanding of the role of VPA in BD.

Proteomic analysis of the postsynaptic density implicates synaptic function and energy pathways in bipolar disorder

“…We also compared our findings with data from recently published articles of chronic treatment of rats with lithium or valproate. 68 , 69 , 70 Nanavati et al 69 used proteomic methods to assess the PSD-enriched hippocampus following chronic treatment with lithium or valproate. Overall, there was little overlap with our findings, although they did observe dysregulation of ANK3, IGSF8 and CAPZB in the same direction as observed by us, suggesting that their findings may be drug treatment-related.…”