Adult neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells located in specific area of the central nervous system (CNS). The age-related incidence of many CNS diseases coincides with a reduced adult neurogenic potential. The regenerative capabili- ty and the amount of adult neural stem cells (aNSC), in fact, decline with age, contributing to the reduced functionality of the aged brain. Despite the great interest in age related diseases, in Italy alone over-65 people will rise to the 18% value of 2010 to more than 30% in 2050, the molecular factors responsible for age-dependent decay of neural stem cell function are almost unknown. We envisage that genes controlling age-dependent processes act in continuity between development, adulthood and aging. The starting point of our work was a list of brain age- regulated mRNAs that we have previously obtained by RNA-Seq and validated by qPCR and in situ hybridization. 1 Among them, we are currently studying the expression profile and the function of Mex3A and Znf367 genes, codifying respectively for a RNA binding protein and a transcription factor, in embryonic neuro- genesis. These genes, of unknown function, are expressed in neu- roblasts and retinoblasts of Zebrafish and Xenopus laevis embryos and in the aNSC of the short-lived fish Nothobranchius furzeri . By means of gene gain and loss of function approaches in Xenopus and Zebrafish embryos, we started to clarify the spe- cific function of these genes in regulating the maintenance of a stem phenotype in the developing CNS and in regulating survival and differentiation of the primary neurons. The same genes will be tested to verify their function also in neural stem cells of adult fishes. The identification of genetic mechanisms involved in embryonic and adult neurogenesis represents the first step in defining interventions that can increase neurogenesis in the aged brain and that could lead to improved maintenance and even repair of neuronal function.

FUNCTIONAL CHARACTERIZATION OF NOVEL GENES INVOLVED IN BRAIN AGING AND DEVELOPMENT

ORI, MICHELA
2016

Abstract

Adult neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells located in specific area of the central nervous system (CNS). The age-related incidence of many CNS diseases coincides with a reduced adult neurogenic potential. The regenerative capabili- ty and the amount of adult neural stem cells (aNSC), in fact, decline with age, contributing to the reduced functionality of the aged brain. Despite the great interest in age related diseases, in Italy alone over-65 people will rise to the 18% value of 2010 to more than 30% in 2050, the molecular factors responsible for age-dependent decay of neural stem cell function are almost unknown. We envisage that genes controlling age-dependent processes act in continuity between development, adulthood and aging. The starting point of our work was a list of brain age- regulated mRNAs that we have previously obtained by RNA-Seq and validated by qPCR and in situ hybridization. 1 Among them, we are currently studying the expression profile and the function of Mex3A and Znf367 genes, codifying respectively for a RNA binding protein and a transcription factor, in embryonic neuro- genesis. These genes, of unknown function, are expressed in neu- roblasts and retinoblasts of Zebrafish and Xenopus laevis embryos and in the aNSC of the short-lived fish Nothobranchius furzeri . By means of gene gain and loss of function approaches in Xenopus and Zebrafish embryos, we started to clarify the spe- cific function of these genes in regulating the maintenance of a stem phenotype in the developing CNS and in regulating survival and differentiation of the primary neurons. The same genes will be tested to verify their function also in neural stem cells of adult fishes. The identification of genetic mechanisms involved in embryonic and adult neurogenesis represents the first step in defining interventions that can increase neurogenesis in the aged brain and that could lead to improved maintenance and even repair of neuronal function.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/814833
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