Abstract:
:Although depression is a severe and life-threatening psychiatric illness, its pathogenesis still is essentially unknown. Recent studies highlighted the influence of environmental stress factors on an individual's genetic predisposition to develop mood disorders. In the present study, we employed a well-validated stress-induced animal model of depression, Learned Helplessness paradigm, in rats. Learned helpless (LH) and non-learned helpless (NLH) rats were treated with nortriptyline, a tricyclic antidepressant. The resulting 4 groups (LH vs. NLH, treated vs. non-treated), were subjected to global analysis of protein expression, a powerful approach to gain insight into the molecular mechanisms underlying vulnerability to psychiatric disorders and the long-term action of drug treatments. Many of the biological targets of antidepressant drugs are localized at synapses. Thus, to reduce the complexity of the proteome analyzed and to enrich for less abundant synaptic proteins, purified nerve terminals (synaptosomes) from prefrontal/frontal cortex (P/FC) and hippocampus (HPC) of LH-NLH rats were used. Synaptosomes were purified by differential centrifugation on Percoll gradients and analyzed by two-dimensional polyacrylamide gel electrophoresis (2-DE). Protein spots differently regulated in the various comparisons were excised from gels and identified by mass spectrometry. Proteins involved in energy metabolism and cellular remodeling were primarily dysregulated, when LH and NLH rats were compared. Moreover, several proteins (aconitate hydratase, pyruvate dehydrogenase E1, dihydropyrimidinase-related protein-2 and stathmin) were found to be regulated in opposite directions by stress and drug treatment. These proteins could represent new molecular correlates of both vulnerability to stress and response to drugs, and putative targets for the development of novel drugs with antidepressant action. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Mallei A,Giambelli R,Gass P,Racagni G,Mathé AA,Vollmayr B,Popoli Mdoi
10.1016/j.neuropharm.2010.12.012subject
Has Abstractpub_date
2011-06-01 00:00:00pages
1243-53issue
7-8eissn
0028-3908issn
1873-7064pii
S0028-3908(10)00347-3journal_volume
60pub_type
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