The pineal gland beyond melatonin: N-acetylserotonin a new hormone of the dark?

• Grant number: 19/03348-4
• Support type: Regular Research Grants
• Duration: July 01, 2019 - September 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology
• Principal researcher: Regina Pekelmann Markus
• Grantee: Regina Pekelmann Markus
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Zulma Felisbina da Silva Ferreira

Abstract

The pineal gland is a unique structure of ectodermal origin, whose hormone melatonin, is also known as dark hormone, because it tells the internal environment the duration of the night. This gland is also integrated with the body's defense processes, since it negatively regulates the migration of leukocytes to peripheral tissues and the production of pro-inflammatory agents by several cells. The production of melatonin by pineal is suppressed at the beginning of an acute inflammatory response. The precursor molecule of melatonin, N-acetylserotonin (NAS), acting on its own receptors (TrkB), also has anti-inflammatory and neuroprotective properties. When assembling an inflammatory response, it is the enzyme that converts serotonin into melatonin which is suppressed. However, when there is an increase in the order of 5 log units of the ATP concentration, which can be obtained under conditions of necroptosis or necrosis, the inhibition of the enzyme converting NAS into melatonin occurs. Our goal in this project is to check if under these conditions NAS could be the dark hormone. ATP and selective agonists of P2Y1 and P2X7 receptors administered by the intracerebroventricular (i.c.v) route will be tested and as a result the concentration of NAS and melatonin in the pineal and the cytoprotective effect will be determined by determining the concentration of cytokines and cell death in the cortex and cerebellum. This is an innovative project from a conceptual point of view that aims to demonstrate that besides melatonin, the precursor NAS, is also a hormone released by the pineal. (AU)