Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Silvia Mori is active.

Publication


Featured researches published by Silvia Mori.


Journal of Psychiatric Research | 1998

cAMP-dependent phosphorylation system after short and long-term administration of moclobemide

Silvia Mori; Raffaella Zanardi; Maurizio Popoli; Sara Garbini; Nicoletta Brunello; Enrico Smeraldi; Giorgio Racagni; Jorge Perez

Accumulating evidence suggested that signal transduction cascade including protein phosphorylation is implicated in the neurochemical action of antidepressant agents. Clinical data indicated that moclobemide, a short acting and reversible inhibitor of monoamino oxidase type. A, is an effective antidepressant medication. However, little is known about the intracellular effects of this compound. Thus, in the present study we assessed the binding of cAMP to cAMP-dependent protein kinase (PKA) in rat cerebral cortex following short and long-term administration of moclobemide. The results showed that 21 days of treatment with moclobemide significantly increased the specific [32P]-cAMP covalent binding into the soluble 52-54 kDa cAMP-receptor. This effect was not seen following 1, 5 and 12 days of treatment. These findings suggest that PKA could be implicated in the biochemical effects of moclobemide.


Pharmacology & Therapeutics | 2001

Serine/threonine kinases as molecular targets of antidepressants: implications for pharmacological treatment and pathophysiology of affective disorders

Maurizio Popoli; Silvia Mori; Nicoletta Brunello; Jorge Perez; Massimo Gennarelli; Giorgio Racagni

It is currently a widely accepted opinion that adaptive, plastic changes in the molecular and cellular components of neuronal signaling systems correlate with the effects on mood and cognition observed after long-term treatment with antidepressant drugs. Protein phosphorylation represents a key step for most signaling systems, and it is involved in the regulation of virtually all cellular functions. Two serine/threonine kinases, Ca2+ /calmodulin-dependent protein kinase II and cyclic AMP-dependent protein kinase, have been shown to be activated in the brain following antidepressant treatment. The changes in kinase activity are mirrored by changes in the phosphorylation of selected protein substrates in subcellular compartments (presynaptic terminals and microtubules), which, in turn, may contribute to the modulation of synaptic transmission observed with antidepressants. The molecular consequences of protein kinase activation may account for some of the alterations in neural function induced by antidepressants, and may suggest novel possible strategies of pharmacological intervention.


Journal of Psychiatric Research | 2000

Altered Rap1 endogenous phosphorylation and levels in platelets from patients with bipolar disorder

Jorge Perez; Daniela Tardito; Silvia Mori; Giorgio Racagni; Enrico Smeraldi; Raffaella Zanardi

Previous studies have reported abnormalities either in the cAMP-dependent endogenous phosphorylation or in the levels of Rap1 in platelets from bipolar patients. One limitation of these findings was that they come from different groups of patients in independent studies. To overcome this limitation, we designed the present study in which both these biochemicals parameters were assessed in the same cohort of euthymic bipolar patients and healthy subjects. The results showed that the cAMP-dependent phosphorylation of Rap1 was significantly higher in platelets of bipolar patients with respect to healthy subjects. Furthermore, immunoblotting experiments revealed that also the levels of Rap1 were significantly higher in bipolar patients than in control subjects, thus supporting that the abnormal phosphorylation can be ascribed to the increased levels of Rap1. Taken together the results of the present study further support that downstream components of the cAMP signal cascade could be involved in the pathophysiology of bipolar disorders.


Neuropsychopharmacology | 1998

Effects of Lithium on cAMP-Dependent Protein Kinase in Rat Brain

Silvia Mori; Daniela Tardito; Alessandra Dorigo; Raffaella Zanardi; Enrico Smeraldi; Giorgio Racagni; Jorge Perez

We have investigated the effects of lithium treatment on cAMP-dependent protein kinase in discrete brain areas of rat by using photoaffinity labeling as well as western blotting. Lithium administered for 5 weeks resulted in a significant increase of the cAMP binding to the 52 kDa cAMP-receptor in the soluble, but not in the particulate, fractions of both hippocampus and frontal cortex. Moreover, immunoblotting experiments revealed that chronic lithium treatment significantly increased the immunoreactivity against the regulatory and the catalytic subunits of the cAMP-dependent protein kinase in the soluble fraction of both brain areas. In contrast, no appreciable effect was observed in the particulate fractions. Short-term lithium treatment induced a significant increase in the immunolabeling of the catalytic subunits in the soluble fraction of both areas; whereas, the regulatory subunits and the actin were unchanged. In the particulate fractions, short-term lithium treatment did not elicit any substantial modification. Taken together, the results of the present study add to the growing evidence indicating that components of the cAMP signalling could play a crucial role in the biochemical action of lithium.


Life Sciences | 1996

Inhibitory effect of lithium on cAMP dependent phosphorylation system

Silvia Mori; Raffaella Zanardi; Maurizio Popoli; Enrico Smeraldi; Giorgio Racagni; Jorge Perez

The aim of the present study was to assess the direct effect of lithium on cAMP dependent phosphorylation. The results show that lithium, but not rubidium, at therapeutic and high concentrations significantly decreases the cAMP stimulated MAP2 endogenous phosphorylation in microtubule fraction. An inhibitory effect of lithium has also been found using purified heat stable microtubule proteins phosphorylated by the catalytic subunit of PKA. These data suggest a direct effect of lithium on the cAMP dependent protein kinase.


European Neuropsychopharmacology | 1995

Effects of fluvoxamine on the protein phosphorylation system associated with rat neuronal microtubules.

Jorge Perez; Silvia Mori; M. Caivano; Maurizio Popoli; Raffaella Zanardi; Enrico Smeraldi; G Racagnib

We have studied the phosphorylation system associated with the rat cerebrocortical microtubule fraction after short- and long-term administration (15 mg/kg) of fluvoxamine, a selective serotonin reuptake inhibitor with antidepressant activity. Fluvoxamine administered for 5 days significantly enhanced the 32P incorporation stimulated by cAMP into MAP2, while it failed to produce this effect after 12 and 21 days. Moreover, in the same periods of treatment no changes were observed in basal phosphorylation and in the pattern of microtubule proteins. In conclusion, our results suggest that changes in the protein phosphorylation system associated with the microtubule fraction could represent an early neurochemical modification involved in the action of fluvoxamine.


Journal of Affective Disorders | 2003

Protein kinase A activity in platelets from patients with bipolar disorder

Daniela Tardito; Silvia Mori; Giorgio Racagni; Enrico Smeraldi; Raffaella Zanardi; Jorge Perez

BACKGROUND Abnormal levels of protein kinase A (PKA) were found in patients with bipolar disorder (BD). Since altered levels are generally accompanied by functional modifications, the purpose of this study was to investigate PKA activity in patients with BD. METHODS PKA activity was assessed in platelets from 20 drug-free bipolar patients and 19 controls. RESULTS The cAMP-stimulated PKA activity was significantly increased in bipolar patients compared with controls. LIMITATIONS This study made use of platelets, which may not fully represent changes occurring in specific brain regions. CONCLUSION This study adds to the growing evidence suggesting that abnormalities of PKA are associated with BD.


Neuropharmacology | 1998

Modifications in brain cAMP- and calcium/calmodulin-dependent protein kinases induced by treatment with S-adenosylmethionine

S Zanotti; Silvia Mori; R Radaelli; Jorge Perez; Giorgio Racagni; Maurizio Popoli

Several lines of evidence suggest that the mechanism of action of antidepressant drugs (AD) involves adaptive changes occurring in intraneuronal post-receptor signal transduction cascades. Protein phosphorylation has a key role in signal transduction and was previously found to be a target in the action of AD (5-HT and/or NA reuptake blockers). Several studies showed that cAMP- and type II Ca2+/calmodulin-dependent protein kinases (PKA and CaMKII) are markedly affected by typical AD in two different and complementary cellular districts, respectively microtubules (a somatodendritic compartment) and synaptic vesicles (a presynaptic terminal compartment). In order to investigate whether the effect on protein kinases may be involved in the therapeutic action of drugs it is interesting to compare the effect of atypical AD with that of typical drugs. In this study the effect of the atypical AD S-adenosylmethionine (SAMe) was tested. Repeated (12 days) SAMe treatment induced in cerebrocortical microtubules an increase in the binding of cAMP to the RII PKA regulatory subunit and an increase in the endogenous phosphorylation of microtubule-associated protein 2, an effect resembling that of typical AD. In synaptic terminals the treatment induced an increase in the activity of CaMKII and in the endogenous phosphorylation of vesicular substrates. However, this modification was found in the cerebral cortex rather than in the hippocampus, where typical AD affect CaMKII. In addition the synapsin I level was decreased in the hippocampus and increased in the cerebral cortex, an effect not detected with typical AD.


The International Journal of Neuropsychopharmacology | 1998

Time-course changes in rat cerebral cortex subcellular distribution of the cyclic-AMP binding after treatment with selective serotonin reuptake inhibitors.

Silvia Mori; Sara Garbini; Matilde Caivano; Jorge Perez; Giorgio Racagni

Pharmacological investigations have suggested the involvement of the cAMP transduction pathway in the action of antidepressant drugs and in the pathophysiology of mood disorders. We have extended these studies to determine the time-related effects of two selective serotonin reuptake inhibitors, fluvoxamine (15 mg/kg) and paroxetine (5 mg/kg), on the cAMP-binding in rat cerebral cortex, after short and long-term treatments. Photoaffinity labelling experiments with 8-N(3)-[(32)P]cAMP were carried out in cerebrocortical soluble (S1 or S2) and microtubule fractions. In our conditions, both SSRIs administered for 5 days were unable to affect the cAMP-binding in S1, S2, and in microtubule fractions. After 12 days of treatment, paroxetine and fluvoxamine significantly enhanced the cAMP-binding to the 54 kDa protein, corresponding to the type II regulatory subunit of PKA (RII), in the S1 and microtubule fractions. Any modification in respect to controls was observed in S2, the soluble fraction devoid of microtubules. After 21 days of treatment no changes were observed in the soluble S1 fraction and in microtubules, but the cAMP-binding to the RII subunit was found to be significantly higher in the S2 fraction. The high concentration of RII, demonstrated first in microtubules (12 days) and then in the cytosol (21 days), could be the result of a time-related effect of SSRIs on PKA and its translocation from microtubule compartment to the cytosol. The present findings seem to demonstrate the capacity of SSRIs to modulate the subcellular distribution of PKA and support the involvement of the cAMP pathway in the mechanism of action of these drugs.


Neuropharmacology | 2001

Effect of reboxetine treatment on brain cAMP- and calcium/calmodulin-dependent protein kinases

Silvia Mori; Maurizio Popoli; Nicoletta Brunello; Giorgio Racagni; Jorge Perez

Previous studies showed that the type II Ca(2+)/calmodulin- and cAMP-dependent protein kinases (CaMKII and PKA) are affected by long-term antidepressant treatment in presynaptic and somatodendritic compartments, respectively. This study describes the long-term effects of the selective noradrenaline reuptake inhibitor reboxetine on PKA and CaMKII, in both the microtubule and subsynaptosomal fractions of rat brain. Unlike other antidepressants, chronic reboxetine induced in the cerebrocortical soluble and microtubule fractions a decrease in the [(32)P]cAMP binding to the type II PKA regulatory subunit. No change in the cAMP-dependent endogenous phosphorylation of the protein substrate, microtubule-associated protein 2 was observed. In the hippocampal subsynaptosomal fractions (synaptic vesicles and synaptosomal membranes) reboxetine induced a robust increase in the activity but not in the expression of CaMKII. An increase in the calcium/calmodulin-dependent phosphorylation of presynaptic substrates was also detected. These findings showed that reboxetine modulates post-receptor signal transduction systems in rat brain.

Collaboration


Dive into the Silvia Mori's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Raffaella Zanardi

Vita-Salute San Raffaele University

View shared research outputs
Top Co-Authors

Avatar

Enrico Smeraldi

Vita-Salute San Raffaele University

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Nicoletta Brunello

University of Modena and Reggio Emilia

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge