Dataset Information

The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome.

ABSTRACT: 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.

SUBMITTER: Nanavati D

PROVIDER: S-EPMC3192943 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome.

Nanavati Dhaval D Austin Daniel R DR Catapano Lisa A LA Luckenbaugh David A DA Dosemeci Ayse A Manji Husseini K HK Chen Guang G Markey Sanford P SP

Journal of neurochemistry 20110921 3

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 ...[more]

PMID: 21838781

Similar Datasets

Project description:This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically administered lithium, carbamazepine, valproate, or lamotrigine each downregulated brain AA metabolism, and it is consistent with reported upregulated AA cascade markers in post-mortem BD brain. In the rats, each mood stabilizer reduced AA turnover in brain phospholipids, cyclooxygenase-2 expression, and prostaglandin E2 concentration. Lithium and carbamazepine also reduced expression of cytosolic phospholipase A2 (cPLA2) IVA, which releases AA from membrane phospholipids, whereas valproate uncompetitively inhibited in vitro acyl-CoA synthetase-4, which recycles AA into phospholipid. Topiramate and gabapentin, proven ineffective in BD, changed rat brain AA metabolism minimally. On the other hand, the atypical antipsychotics olanzapine and clozapine, which show efficacy in BD, decreased rat brain AA metabolism by reducing plasma AA availability. Each of the four approved mood stabilizers also dampened brain AA signaling during glutamatergic NMDA and dopaminergic D2 receptor activation, while lithium enhanced the signal during cholinergic muscarinic receptor activation. In BD patients, such signaling effects might normalize the neurotransmission imbalance proposed to cause disease symptoms. Additionally, the antidepressants fluoxetine and imipramine, which tend to switch BD depression to mania, each increased AA turnover and cPLA2 IVA expression in rat brain, suggesting that brain AA metabolism is higher in BD mania than depression. The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients.

Dataset Information

The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome.

Publications

The effects of chronic treatment with mood stabilizers on the rat hippocampal post-synaptic density proteome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets