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Cellular and molecular basis of the acquisition and extinction of conditioned suprression: targets of action of standardized extrato of Ginkgo biloba

Grant number: 13/20378-8
Support type:Regular Research Grants
Duration: March 01, 2014 - October 31, 2016
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Suzete Maria Cerutti
Grantee:Suzete Maria Cerutti
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
Assoc. researchers:Janete Maria Cerutti ; Monica Marques Telles

Abstract

The major research interest of our laboratory is to gain substantial knowledge on the molecular and cellular basis underlying the acquisition and extinction of conditioned fear, which will enable the understanding of changes previously described by our group after treatment with the standardized extract of Ginkgo biloba L. (EGb). Additionally, this study may provide new pharmacological approaches for the treatment of cognitive deficits or disorders related to inability to adequately suppress fear, as in anxiety. Several studies have suggested that glutamatergic, gabaergic or serotoninergic neurotransmission are major strategic targets for these treatments. Thus, this study aims to analyze the protein expression of NR2B subunit of the NMDA receptor, GABAA receptor and serotonin 5-HT1A receptor in the dorsal hippocampus, the amygdaloid complex and the prefrontal cortex of rats submitted to the acquisition and extinction of conditioned emotional response (CER) and acute treatment with EGb. The involvement of different systems in the conditioned fear will be evaluated by analysis of the brains of rats treated with EGb with a single dose of EGb (250 mg.Kg-1 500 mg.Kg-1 or 1000 mg.Kg-1) and/or specific antagonists of the NMDA glutamate receptor (NR2B, RO 256981 10 mg. kg-1), GABA (Picrotoxin, 0.75 mg.Kg-1) and the 5-HT1A serotonin receptor (SWAY 100135, 0.3 mg.Kg-1) or agonists (NMDA, Diazepam and Buspirone) and vehicle solutions (saline or Tween) and tested in a subsequent CER procedure. Treatment were administered before the training or prior to the tests made 48, 72, or 96 hours after conditioning for analysis of changes in the acquisition, consolidation or fear extinction. 24 hours after acquisition of conditioned fear (Test1) or extinction training (Test 2) or extinction test (Test 3). The brain of the rats treated or/and fear conditioned were perfused with 4% formalin buffered (0.1 M phosphate) and was removed and were kept for cryoprotection in 20% sucrose for 48 hours at. For immunohistochemical analysis, proposed in this study, will be used antibodies against the proteins in study. Still, the identification of neural cell (neuron or astrocytes), involved in the neurochemical changes suggested here, may help us to understand the phenomena. Thus, by using antibodies to glial fibrillary acidic protein (anti-GFAP) or neurofilament protein (anti-NF) simultaneously to receptor analysis by immunofluorescence double stain can give us informations about the interaction between the cell types and the differential expression of receptors. Further, the contribution of the HD in the fear acquisition and/or maintenance of conditioned suppression will evaluate in the HD samples of naive, trained and treated animals 24 hours or 40 days after training by proteomic analysis. For the quantitative analysis of protein expression from different receivers will be used one-way ANOVA followed by the Bonferroni test. (AU)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZAMBERLAM, CLAUDIA R.; TILGER, MYRCEA A. S.; MORAES, LAIS; CERUTTI, JANETE M.; CERUTTI, SUZETE M. Ginkgo biloba treatments reverse the impairment of conditioned suppression acquisition induced by GluN2B-NMDA and 5-HT1A receptor blockade: Modulatory effects of the circuitry of the dorsal hippocampal formation. Physiology & Behavior, v. 209, OCT 1 2019. Web of Science Citations: 0.
GAIARDO, RENAN BARRETTA; ABREU, THIAGO FERREIRA; TASHIMA, ALEXANDRE KEIJI; TELLES, MONICA MARQUES; CERUTTI, SUZETE MARIA. Xiaochaihutang Inhibits the Activation of Hepatic Stellate Cell Line T6 Through the Nrf2 Pathway. FRONTIERS IN PHARMACOLOGY, v. 9, JAN 7 2019. Web of Science Citations: 0.
ZAMBERLAM, C. R.; VENDRASCO, N. C.; OLIVEIRA, D. R.; GAIARDO, R. B.; CERUTTI, S. M. Effects of standardized Ginkgo biloba extract on the acquisition, retrieval and extinction of conditioned suppression: Evidence that short-term memory and long-term memory are differentially modulated. Physiology & Behavior, v. 165, p. 55-68, OCT 15 2016. Web of Science Citations: 1.
DE OLIVEIRA, DANIELA R.; ZAMBERLAM, CLAUDIA R.; REGO, GIZELDA M.; CAVALHEIRO, ALBERTO; CERUTTI, JANETE M.; CERUTTI, SUZETE M. Effects of a Flavonoid-Rich Fraction on the Acquisition and Extinction of Fear Memory: Pharmacological and Molecular Approaches. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, v. 9, JAN 5 2016. Web of Science Citations: 4.

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