Evaluation of the neuroprotective and anti-inflammatory effect of caffeine in a murine model of LPS-induced neuroinflammation

• Grant number: 20/13436-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): January 01, 2021
• Effective date (End): December 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Rodrigo Augusto da Silva
• Grantee: Paula Lemes dos Santos Sanna
• Home Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade de Taubaté (UNITAU). Taubaté , SP, Brazil

Abstract

Caffeine is a natural alkaloid with the most consumed psychoactive property in the world that is present in several drinks and foods. Due to its hydrophobic properties, caffeine is quickly distributed throughout the body and can cross all biological membranes including the Blood-brain Barrier (BBB). This biochemical characteristic guarantees the observed psychostimulant effects, which are produced preferentially by the antagonistic action of Adenosine Receptors (ARs). Thus, it is a common consensus that the beneficial effects of caffeine consumption are predominantly due to the action on ARs. Although caffeine exerts its action predominantly through non-selective antagonism of brain adenosine receptors, numerous studies have demonstrated its potential as an epigenetic modulating agent by increasing the gene expression of enzymes involved in DNA methylation. However, information about the effect of caffeine on the epigenetic control of genes encoding adenosine receptors is limited. Thus, this proposal aims to investigate the molecular mechanisms involved in the neuroprotective effect of caffeine pretreatment (6 mg / kg) mainly related to the transcriptional control of ADORA 1 and ADORA2A genes mediated by DNA methylation 24 h after induction of neuroinflammation by intraperitoneal (ip) administration of lipopolysaccharide (LPS).