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Title/Abstract/Keywords

PKC BETA AS A NEW THERAPY TARGET ON PREVENTION OF WEIGHT GAIN DURING LONG-TERM ATYPICAL ANTIPSYCHOTICS TREATMENT

Ioannidi, Elli (2015) PKC BETA AS A NEW THERAPY TARGET ON PREVENTION OF WEIGHT GAIN DURING LONG-TERM ATYPICAL ANTIPSYCHOTICS TREATMENT. PhD Thesis , Università degli Studi di Ferrara.

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    Abstract

    Atypical antipsychotics (APDs) are currently used in clinical practice for a variety of mental disorders (schizophrenia, bipolar disorder, severe behavioral disorder) presenting as common side effects the weight gain, obesity, lipid abnormalities and diabetes. Our previous studies in vitro on adipogenic events, show that in cell cultures of human pre-adipocytes and rat muscle-derived stem cells, where APDs (clozapine, olanzapine, quetiapine, risperdione and aripiprazole) were added in the presence of high glucose, presented an increase in lipid accumulation and an enhancement of pre-adipocyte differentiation. Our data show that Protein Kinase C isoform β (PKC β) has a crucial role in the metabolic pathways leading to the neo-differentiation of adipose cells during APDs treatment. The pharmacological inhibition and the molecular silencing of PKC-β prevent the APDs-induced lipid accumulation, providing its direct involvement into this process. Atypical antipsychotics (APDs) are currently used in clinical practice for a variety of mental disorders presenting as common side effect the weight gain, obesity, lipid abnormalities and diabetes. In the present study, our data show that Clozapine induces weight gain at the mice after chronic treatment. The average of the weight in PKC b null mice was not increased after the treatment with Clozapine, according to our data where PKC b is activated in vitro by the APDs and implicated in the metabolic pathway leading to the neo-differentiation of adipose cells. We also show that the pharmacological inhibition of PKCβ prevented the weight gain on mice treated with Clozapine. To evaluate if the therapeutic effect of Clozapine was maintained also in PKC b null mice and in the group of mice treated with the pharmacological inhibitor of PKCβ, we performed three different motor tests, to all animal groups.

    Item Type:Thesis (PhD Thesis)
    Date:20 March 2015
    Tutor:Tognon, Mauro - Pinton, Paolo - Rimessi, Alessandro
    Coordinator:Capitani, Silvano
    Institution:Università degli Studi di Ferrara
    PhD:XXVII Anno 2012 > SCIENZE BIOMEDICHE
    Divisions:Dipartimento > Morfologia ed embriologia
    Subjects:Area 05 - Scienze biologiche > BIO/13 Biologia applicata
    Uncontrolled Keywords:PKC beta, atypical antipsychotics, weight gain, clozapine
    Deposited on:22 Jul 2015 14:50

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