Recent studies showed an important influence of stress, such as adverse life events, on an individually variable background of genetic vulnerability. The Flinders Sensitive Line (FSL) rats are a validated model of depression carrying genetic vulnerability associated to distinct features of pathology. FSL and Flinders Resistant Line (FRL, the corresponding control) rats were subjected to a maternal separation (MS) protocol in order to investigate the outcome of gene–environment interaction. Treatment with the antidepressant escitalopram was carried out at weeks 11–14 of age. Purified synaptosomes were analyzed by two-dimensional polyacrylamide gel electrophoresis (2DE). Statistical analysis of 2DE maps from P/FC synaptosomes revealed 37 proteins differently regulated in FSL vs. FRL rats. Stress of MS significantly dysregulated 48 proteins in FSL, and 24 proteins in FRL P/FC synaptosomes. Chronic escitalopram treatment differently regulated 33 protein spots in FSL, and 7 protein spots in FSL subjected to MS. Interestingly, in FSL rats 3 of the proteins down-regulated by MS, were up-regulated by escitalopram treatment. In addition, protein phosphorylation, the most frequent posttranslational modification of protein, was investigated in the same subcellular fractions. Ca2+/calmodulin-dependent kinase II (CaMKII) and extracellular signal-regulated kinases 1/2 (ERK1/2) are protein kinases that have been involved in molecular mechanisms regulating synaptic plasticity. Our results show that FSL and FRL rats displayed an opposite profile of activation for the two kinases investigated, suggesting that basic vulnerability is associated with signalling dysfunction and that postnatal early events aggravate this dysfunction.

Functional proteomic analysis of an animal model of depression combining genetic vulnerability and environmental stress / Mallei A.; Giambelli R.; Barbiero V.S.; Mathé A.A.; El Khoury A.; Carboni L.; Domenici E.; Aitchison K.J.; Racagni G.; Popoli M.. - In: EUROPEAN NEUROPSYCHOPHARMACOLOGY. - ISSN 0924-977X. - STAMPA. - 16, supplement 4:(2006), pp. S169-S170. (Intervento presentato al convegno European College of Neuropsychopharmacology Meeting tenutosi a Paris, France nel September 16-20, 2006) [10.1016/S0924-977X(06)70028-1].

Functional proteomic analysis of an animal model of depression combining genetic vulnerability and environmental stress.

CARBONI, LUCIA;
2006

Abstract

Recent studies showed an important influence of stress, such as adverse life events, on an individually variable background of genetic vulnerability. The Flinders Sensitive Line (FSL) rats are a validated model of depression carrying genetic vulnerability associated to distinct features of pathology. FSL and Flinders Resistant Line (FRL, the corresponding control) rats were subjected to a maternal separation (MS) protocol in order to investigate the outcome of gene–environment interaction. Treatment with the antidepressant escitalopram was carried out at weeks 11–14 of age. Purified synaptosomes were analyzed by two-dimensional polyacrylamide gel electrophoresis (2DE). Statistical analysis of 2DE maps from P/FC synaptosomes revealed 37 proteins differently regulated in FSL vs. FRL rats. Stress of MS significantly dysregulated 48 proteins in FSL, and 24 proteins in FRL P/FC synaptosomes. Chronic escitalopram treatment differently regulated 33 protein spots in FSL, and 7 protein spots in FSL subjected to MS. Interestingly, in FSL rats 3 of the proteins down-regulated by MS, were up-regulated by escitalopram treatment. In addition, protein phosphorylation, the most frequent posttranslational modification of protein, was investigated in the same subcellular fractions. Ca2+/calmodulin-dependent kinase II (CaMKII) and extracellular signal-regulated kinases 1/2 (ERK1/2) are protein kinases that have been involved in molecular mechanisms regulating synaptic plasticity. Our results show that FSL and FRL rats displayed an opposite profile of activation for the two kinases investigated, suggesting that basic vulnerability is associated with signalling dysfunction and that postnatal early events aggravate this dysfunction.
2006
Papers of the 19th ECNP Congress
S169
S170
Functional proteomic analysis of an animal model of depression combining genetic vulnerability and environmental stress / Mallei A.; Giambelli R.; Barbiero V.S.; Mathé A.A.; El Khoury A.; Carboni L.; Domenici E.; Aitchison K.J.; Racagni G.; Popoli M.. - In: EUROPEAN NEUROPSYCHOPHARMACOLOGY. - ISSN 0924-977X. - STAMPA. - 16, supplement 4:(2006), pp. S169-S170. (Intervento presentato al convegno European College of Neuropsychopharmacology Meeting tenutosi a Paris, France nel September 16-20, 2006) [10.1016/S0924-977X(06)70028-1].
Mallei A.; Giambelli R.; Barbiero V.S.; Mathé A.A.; El Khoury A.; Carboni L.; Domenici E.; Aitchison K.J.; Racagni G.; Popoli M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/118524
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