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Neuroanatomic characterization and dimorphic aspects of ECRG4 / AUGURIN in rats (Rattus Norvegicus - Long-Evans) during the aging process

Grant number: 19/01820-8
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2019
Effective date (End): April 30, 2021
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Jackson Cioni Bittencourt
Grantee:Isis Fieri
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Augurin is a peptide that has recently been identified that is encoded by the gene related to esophageal cancer-4 (ECRG4), a gene highly conserved in vertebrates. In the literature it has been associated with cancer, as a tumor suppressor gene/metastasis; senescence and aging of the neural cell; central nervous system (CNS) homeostasis; injury and immune responses. Augurin is produced by post-translational processing of the 148 amino acid ECRG4 protein and in rodents is present mainly in the esophagus, stomach, skeletal muscle, heart, uterus, bladder, adrenal gland and thyroid epithelial cells. In the CNS, the choroid plexus has the highest gene expression, but it is also present in the hypothalamus, olfactory bulb, pituitary and cerebellum. Because it is a relatively new peptide, the neuroanatomic aspects are not fully elucidated, especially regarding aging and gender differences. Thus, it is proposed to evaluate the role of augurin as a neuroendocrine peptide and its presence in the cerebrospinal fluid (CSF) in the senescence process. For this, young, adult and elderly rats of both sexes will be evaluated: immunoreactivity to augurin in the brain by immunohistochemistry; serum levels of augurin by ELISA; the levels of ECRG4 encephalic gene expression by RT-PCR; the total protein concentration in the CSF, by the colorimetric technique of protein quantification with pyrogallol red and the concentration of augurin in the CSF by ELISA. Statistical analysis will be performed by analysis of variance (ANOVA) followed by the Tukey-Kramer multiple comparisons test or Kruskal-Wallis non-parametric test, considering p < 0.05.