Molecular interactions between CB1 and TrkB modulating repetitive behavior

• Grant number: 13/01029-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 01, 2013
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Plínio Cabrera Casarotto
• Supervisor: Eero Hemminki Castrén
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Helsinki, Finland
• Associated to the scholarship: 11/02746-4 - Involvement of endocannabinoid system modulating repetitive behavior: possible participation of brain-derived neurotrophic factor (BDNF), BP.PD

Abstract

The malfunction of cortico-striatum-thalamic-cortical (CSTC) circuitry is involved in several neuropsychiatric disorders, specially obsessive-compulsive disorder (OCD). The observation that OCD patients improve following treatment with selective serotonin re-uptake inhibitors (SSRI) leaded to implicate this system in this pathology. However OCD pharmacotherapy is effective in less than half of the patients. In this scenario new pharmacological approaches are necessary. Recently was observed that CB1-facilitating drugs exert anticompulsive-like effects in animal models. Activating CB1 receptors in cortical cultured cells leads to TRKB coupling and activation. It is still unclear if CB1-TRKB interaction occurs in CSTC of adult animals as well as its possible physiological role. Thus, the present project aims to evaluate the interaction between endocannabinoid and BDNF/TRKB systems modulating repetitive behaviors. We intend to submit BDNF/TRKB system transgenic animals to models predictive of anticompulsive-like effect and the effects of CB1-activating drugs. We will also investigate in vitro interactions between CB1 and TRKB. To this aim, we will treat cortical and striatal primary cultured cells to CB1 agonist. In order to determine if the CB1-dependent TRKB activation depends on BDNF release we will evaluate the levels of CB1-mediated TRKB activation in CB1 or BDNF silenced HiB5 cells. (AU)

Scientific publications

(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)

DINIZ, CASSIANO R. A. F.; BIOJONE, CAROLINE; JOCA, SARNIA R. L.; RANTAMAKI, TOMI; CASTREN, EERO; GUIMARAES, FRANCISCO S.; CASAROTTO, PLINIO C.. Dual mechanism of TRKB activation by anandamide through CB1 and TRPV1 receptors. PeerJ, v. 7, FEB 21 2019. (13/02549-0, 18/04250-5, 11/02746-4, 13/01029-2)