Effects of sleep deprivation in adenosine signaling in the hippocampus

• Grant number: 15/18605-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2016
• End date: August 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Débora Cristina Hipólide
• Grantee: Débora Cristina Hipólide
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

A great research interest in our studies is related to the deleterious effects of sleep loss produces, specifically cognitive functions such as memory. An interesting result obtained in our laboratory indicates that sleep deprivation (PS) in rats before aversive learning task produces animal performance impaired. Motivated by the results found and the search of the mechanisms associated with impaired performance on learning and memory tasks after PS, a series of investigations to evaluate the participation of systems known to modulate the learning behavior, memory and sleep have been conducted. The proposed continuation of this approach directs research on the participation of the adenosine system as an important modulator of this phenomenon triggered by sleep deprivation. From the biochemical point of view, sleep deprivation increases extracellular levels of adenosine as well as changes in various regions of the central nervous system, levels of adenosine receptors and activity of ectonucleotidases, enzymes responsible for their production. Adenosine has known effect on memory and the effects of A1 receptor activation often cause memory impairment, whereas activation of A2A receptors generally leading to an advantage in memory processing. One of the ways by which adenosine acts on the central nervous system is modulation of other neurotransmitter systems, including glutamatergic system. We aim to investigate the role of adenosine in the memory loss caused by sleep deprivation. Results already obtained in the course of this project show that acute treatment with DPCPX, an antagonist of A1 receptors, prevents the loss in consolidation caused by sleep deprivation, demonstrating the role of adenosine on the memory impairment. Specifically, how sleep deprivation affects the expression and activity of ectonucleotidases and adenosine deaminase in the hippocampus. Also test the ability of the CGS 21680, A2A receptor agonist, in preventing the loss of memory caused by sleep deprivation. Finally, we find the effect of sleep deprivation and the aforementioned drugs on the activity of protein kinase A and translocation of AMPA receptors during memory consolidation process. (AU)