Effects of neuroinflammation on Sonic Hedgehog-mediated signaling in the central nervous system in adult mice

• Grant number: 19/21392-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2020
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Rodrigo Augusto da Silva
• Grantee: Amanda Yasmin Ilario dos Santos
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade de Taubaté (UNITAU). Taubaté , SP, Brazil

Abstract

Sonic Hedgehog (SHH) is characterized by being a secreted glycoprotein which, due to its morphogenic and mitotic properties, controls the pattern of progenitor cell changes and neuronal and glial progeny, especially during development. Its autocrine and paracrine action is extensively studied in the context of embryonic development of the Central Nervous System (CNS). However, the number of studies showing the importance of this active pathway for neurogenesis, hippocampal plasticity and activation of repair/defense systems in the adult brain is increasing; its dysregulation is involved in the pathogenesis of various neurological disorders. On the other hand, neuroinflammation, especially that modulated by the cellular response of astrocytes and microglia, is directly associated with neuron damage in neurodegenerative disorders, such as Parkinson's and Alzheimer's disease. Although the role of the Hh signaling pathway is not well established in neuroinflammation, it is suggested that its activation may be correlated with the activation of defense and repair mechanisms, and the impact of neuroinflammation on the transcriptional control of Hh pathway members for different brain regions still poorly known. Thus, the aim of this study will initially be to characterize the neuroinflammatory effect of intraperitoneal (i.p.) administration of LPS by evaluating gene expression of pro and anti-inflammatory cytokines; and to determine the transcriptional profile of Hh signaling pathway proteins in different brain regions, and to evaluate and compare the effects of the inflammatory response on the control of pathway gene expression. For this will be evaluated the gene expression of inflammatory cytokines; Tnf±, Il-6, Il-1², Il-18, Il-10 and Il-13 and Shh, Ptch1, Sufu and Gli1 proteins by qPCR. With this study, we hope to improve the understanding of the interaction between neuroinflammation and Hh signaling, mainly mediated by Sonic Hedgehog (SHH) in different brain structures and thus guide a better direction of its effective contribution in the adult brain.

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)

COSTA, MARIANA RIBEIRO; ILARIO DOS SANTOS, AMANDA YASMIN; DE MIRANDA, TAIS BROWNE; AIRES, ROGERIO; COQUE, ALEX DE CAMARGO; PEREZ HURTADO, ELIZABETH CRISTINA; BERNARDI, MARIA MARTHA; ARIAS PECORARI, VANESSA GALLEGO; ANDIA, DENISE CARLETO; BIRBRAIR, ALEXANDER; et al. Impact of neuroinflammation on epigenetic transcriptional control of Sonic Hedgehog members in the central nervous system. Brain Research, v. 1799, p. 15-pg., 2023-01-15. (19/21392-0, 19/25772-2)