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Role of connexin 43 in CXCL12 secretion by astrocytes

Grant number: 11/20492-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 01, 2012
Effective date (End): January 31, 2013
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Marimélia Aparecida Porcionatto
Grantee:Marcella Braga da Costa Reis
Supervisor abroad: David Conover Spray
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Research place: Albert Einstein College of Medicine, United States  
Associated to the scholarship:09/05700-5 - STUDY OF THE NEUROGENIC EFFECTS PROMOTED BY MESENCHIMAL STEM CELLS EXPRESSING SDF-1 N-TERMINAL PEPTIDES TRANSPLANTED ON CENTRAL NERVOUS SYSTEM LESION, BP.DR

Abstract

Neural stem cells present in neurogenic niches in the adult brain are recruited to participate in tissue regeneration in response to injury in the CNS. For acute injuries, such as traumatic brain injury or stroke, these cells are able to respond to molecules released at the injury site. Chemokines secreted by astrocytes and immune cells that invade the brain are able to attract neural stem cells that express specific receptors for these cytokines. Among the chemokines that participate in this process is CXCL12, whose receptor, CXCR4, is expressed by neural stem cells. These cells are attracted to the injury site by CXCL12 as part of the regeneration process, but this process is not completely effective, because few cells can arrive at the injured site and survive in the microenvironment of the injury, which is less favorable for cell survival due to the presence neurotoxic molecules secreted locally. As part of developing strategies to improve the regeneration of nerve tissue is necessary to understand the control of production and secretion of CXCL12, as this could be a way to interfere with the regenerative response by increasing the supply of neural stem cells to the site of injury. Recently it was demonstrated that the secretion of CXCL12 by mesenchymal cells is dependent on connexin 43. The objective of this project is to evaluate whether the secretion of CXCL12 by astrocytes would also be dependent on connexin 43, with the intention of the future, develop strategies to control the expression of this chemokine by astrocytes in the CNS lesions. (AU)

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