The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome
Article first published online: 21 SEP 2011
Published 2011. This article is a US Government work and is in the public domain in the USA
Journal of Neurochemistry
Volume 119, Issue 3, pages 617–629, November 2011
How to Cite
Nanavati, D., Austin, D. R., Catapano, L. A., Luckenbaugh, D. A., Dosemeci, A., Manji, H. K., Chen, G. and Markey, S. P. (2011), The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome. Journal of Neurochemistry, 119: 617–629. doi: 10.1111/j.1471-4159.2011.07424.x
- Issue published online: 12 OCT 2011
- Article first published online: 21 SEP 2011
- Accepted manuscript online: 12 AUG 2011 01:36PM EST
- Received January 26, 2011; revised manuscript received August 8, 2011; accepted August 9, 2011.
- ankyrin 3;
J. Neurochem. (2011) 119, 617–629.
Bipolar disorder is a devastating illness that is marked by recurrent episodes of mania and depression. There is growing evidence that the disease is correlated with disruptions in synaptic plasticity cascades involved in cognition and mood regulation. Alleviating the symptoms of bipolar disorder involves chronic treatment with mood stabilizers like lithium or valproate. These two structurally dissimilar drugs are known to alter prominent signaling cascades in the hippocampus, but their effects on the post-synaptic density complex remain undefined. In this work, we utilized mass spectrometry for quantitative profiling of the rat hippocampal post-synaptic proteome to investigate the effects of chronic mood stabilizer treatment. Our data show that in response to chronic treatment of mood stabilizers there were not gross qualitative changes but rather subtle quantitative perturbations in post-synaptic density proteome linked to several key signaling pathways. Our data specifically support the changes in actin dynamics on valproate treatment. Using label-free quantification methods, we report that lithium and valproate significantly altered the abundance of 21 and 43 proteins, respectively. Seven proteins were affected similarly by both lithium and valproate: Ank3, glutamate receptor 3, dynein heavy chain 1, and four isoforms of the 14-3-3 family. Immunoblotting the same samples confirmed the changes in Ank3 and glutamate receptor 3 abundance. Our findings support the hypotheses that BPD is a synaptic disorder and that mood stabilizers modulate the protein signaling complex in the hippocampal post-synaptic density.