NICD and galectin-3 interactions role in triggering a latent neurogenesis program of reactive astrocytes

• Grant number: 18/05846-9
• Support type: Scholarships in Brazil - Master
• Effective date (Start): October 01, 2018
• Effective date (End): September 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Tais Novaki Ribeiro
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 19/16019-9 - Characterization of Notch1, Notch2 and Rbpj roles in the generation of neural stem cells derived from reactive astrocytes., BE.EP.MS

Abstract

After the central nervous system is injured, astrocytes go through a process of activation, which involves cellular changes to promote tissue repair, leading to the generation of reactive astrocytes. One of the changes is astrocyte dedifferentiation, which can be described as the transition of mature astrocytes to a less differentiated state, similar to neural-stem cells. This phenomenon is seen in a subpopulation of reactive astrocytes, and the molecular mechanisms involved in this process are not well known. In this context, the understanding of the process of astrocyte dedifferentiation is necessary for the development of therapeutic strategies that could aim the use of astroglial cells as a source of neural-stem cells throughout the CNS. Recent studies and results achieved by our group suggests that the Notch receptor, involved in neurodevelopment and neurogenic niches maintenance, is a strong candidate to participate in the dedifferentiation process. The literature supports as well that Galectin-3, a lectin overexpressed in lesion conditions, is intrinsically related to reactive astrocytes proliferative capacity and their potential of acquiring neural-stem cells hallmarks in vitro. Bearing the relevance of these two factors for triggering a latent neurogenic program in reactive astrocytes, the present study has the following aims: 1) to evaluate the colocalization of Galectin-3 and Notch in reactive astrocytes in vitro, 2) to evaluate direct interactions between Galectin-3 and Notch in reactive astrocytes in vitro and 3) to evaluate the role of Gal3/ Notch interaction in the acquisition of a neural-stem cell phenotype by reactive astrocytes in vitro.