Fernando Caetano

Federal University of Minas Gerais, Belo Horizonte, Estado de Minas Gerais, Brazil

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Publications (3)7.3 Total impact

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    ABSTRACT: It is well known that dopamine imbalances are associated with many psychiatric disorders and that the dopaminergic receptor D₂ is the main target of antipsychotics. Recently it was shown that levels of two proteins implicated in dopaminergic signaling, Neuronal calcium sensor-1 (NCS-1) and DARPP-32, are altered in the prefrontal cortex (PFC) of both schizophrenic and bipolar disorder patients. NCS-1, which inhibits D₂ internalization, is upregulated in the PFC of both patients. DARPP-32, which is a downstream effector of dopamine signaling, integrates the pathways of several neurotransmitters and is downregulated in the PFC of both patients. Here, we used PC12 cells stably overexpressing NCS-1 (PC12-NCS-1 cells) to address the function of this protein in DARPP-32 signaling pathway in vitro. PC12-NCS-1 cells displayed downregulation of the cAMP/PKA pathway, with decreased levels of cAMP and phosphorylation of CREB at Ser133. We also observed decreased levels of total and phosphorylated DARPP-32 at Thr34. However, these cells did not show alterations in the levels of D₂ and phosphorylation of DARPP-32 at Thr75. These results indicate that NCS-1 modulates PKA/cAMP signaling pathway. Identification of the cellular mechanisms linking NCS-1 and DARPP-32 may help in the understanding the signaling machinery with potential to be turned into targets for the treatment of schizophrenia and other debilitating psychiatric disorders.
    Cellular and Molecular Neurobiology 01/2011; 31(1):135-43. · 2.29 Impact Factor
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    ABSTRACT: Although electroconvulsive therapy (ECT) has been used as a treatment for mental disorder since 1930s, little progress has been made in the mechanisms underlying its therapeutic or adverse effects. The aim of this work was to analyze the expression of DARPP-32 (a protein with a central role in dopaminergic signaling) in striatum, cortex, hippocampus and cerebellum of Wistar rats subjected to acute or chronic electroconvulsive stimulation (ECS). Rats were submitted to a single stimulation (acute) or to a series of eight stimulations, applied one every 48 h (chronic). Animals were killed for collection of tissue samples at time zero, 0.5, 3, 12, 24 and 48 h after stimulation in the acute model and at the same time intervals after the last stimulation in the chronic model. Our results indicated that acute ECS produces smaller changes in the expression of DARPP-32 but, interestingly, chronic ECS increased transient expression of DARPP-32 in several time frames, in striatum and hippocampus, after the last stimulation. Results on the expression of proteins involved in signaling pathways are relevant for neuropsychiatric disorders and treatment, in particular ECT, and can contribute to shed light on the mechanisms related to therapeutic and adverse effects.
    Brain Research 12/2007; 1179:35-41. · 2.88 Impact Factor
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    ABSTRACT: Although electroconvulsive therapy (ECT) has been used as a treatment for mental disorder since 1930s, little progress has been made towards understanding the mechanisms underlying its therapeutic and adverse effects. The aim of this work was to analyze the expression of NCS-1 (neuronal calcium sensor 1, a protein that was found to be altered in post-mortem prefrontal cortex of schizophrenic patients) in striatum, cortex, hippocampus and cerebellum of Wistar rats after acute or chronic electroconvulsive stimulation (ECS). Rats were submitted to a single stimulation (acute) or to a series of eight stimulations, applied one every 48 h (chronic). Animals were killed for collection of tissue samples at time zero, 30 min, 3, 12, 24 and 48 h after stimulation in the acute model and at the same time intervals after the last stimulation in the chronic model. Our results indicated that chronic ECS increased the expression of NCS-1 only in cerebellum. Such results on the expression of proteins involved in signaling pathways that are relevant for neuropsychiatric disorders and treatment, in particular ECT, can contribute to shed light on the mechanisms related to therapeutic and adverse effects.
    Neurochemical Research 02/2007; 32(1):81-5. · 2.13 Impact Factor