Synaptoproteomics of learned helpless rats involve energy metabolism and cellular remodeling pathways in depressive-like behavior and antidepressant response.
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'.
- SourceAvailable from: Alessandra Della RossaAnnals of the Rheumatic Diseases 10/2003; 62(9):904-5. · 9.11 Impact Factor
- Journal of the European Academy of Dermatology and Venereology 04/2004; 18(2):235-6. · 2.69 Impact Factor
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ABSTRACT: To evaluate biomechanical properties of skin in patients with systemic sclerosis (SSc) using the BTC-2000 suction device. Twenty five patients with limited cutaneous SSc (lcSSc), 20 patients with diffuse disease (dcSSc), and 25 age matched healthy controls were evaluated. Viscoelastic deformation (VED, mm), elastic deformation (ED, mm), ultimate deformation (UD, mm), and pressure-deformation ratio (PDR, mm Hg/mm) were measured on the dorsal surface of the forearm, shoulder, and above the trapezius muscle on the back. Indices of skin extensibility (VED, ED, UD) were reduced and resistance to stress (PDR) increased in patients with dcSSc compared with healthy controls, or patients with lcSSc, at all three sites (p<0.001). At all sites, and overall, UD, ED, and VED were lower and PDR was higher at skin score above grade 2, compared with clinically normal skin. For both lcSSc and dcSSc biomechanical differences from controls were found even at sites of clinically normal skin. BTC-2000 is a sensitive tool for clinical evaluation of skin involvement in SSc and may be a valuable adjunct to skin sclerosis score in disease monitoring.Annals of the Rheumatic Diseases 03/2002; 61(3):237-41. · 9.11 Impact Factor