Evaluation of stress responses induced by paradoxical sleep deprivation in rats Wistar: a neurobiological and comparative approach

• Grant number: 14/22218-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2015
• End date: March 01, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Deborah Suchecki
• Grantee: Danilo Alves de Moraes
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 17/06419-4 - Mapping of neuronal activation and CRH/AVP expression in rats deprived of paradoxical sleep: a neurobiological and comparative approach, BE.EP.DR

Abstract

Over decades, the definition of stress has been reworked in an attempt to reach a concept that covers all aspects of this phenomenon. Much has changed since the original idea proposed by Hans Selye in 1936, but there is still no accepted concept throughout the scientific community. We can understand stress as a set of responses, physiological and/or behavioral, of an organism to a challenging stimulus. Overall, the stressors can be classified according to their nature (physical or psychological) and duration/frequency (acute or chronic). Stressors are responsible for generating a set of responses, composed of neural, endocrine, autonomic and behavioral changes, which are coordinated by the central nervous system (CNS). The sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis are the main systems response to stress, however, another perspective to evaluate the stress response involves the perception of the stimulus by the brain, which is able to discriminate between physical or psychological stimuli and promote the activation of specific pathways. In rodents, paradoxical sleep deprivation (PSP), using the method of single platform, triggers stress responses. However, there is a recurrent critical of these results, that questions if these changes are due to the suppression of paradoxical sleep or other stressors linked to the method. Other methods of PSP promote stress responses similar to those described by the single platform method, varying in the magnitude of the results, leading us to propose that the loss of paradoxical sleep is a stressor stimulus and the PSP per se is responsible for these changes. Thus, the objective of this work is to characterize the PSP as a stress model by comparing its neuronal and endocrine changes with other models of stress. Will be used as methods of stress: cold (physical stressor), predator odor (psychological stressor) and restricted movements (physical stressor and psychological stressor); PSP will be performed by the single platform method. The stimuli will be applied in acute (just one day) or chronic (for four days) form to investigate the differences between the exposure time and the possible existence of habituation. Will be evaluated the activations of SNS (plasma concentrations of adrenaline and noradrenaline) and HPA axis (CRH immunoreactivity in hypothalamus and plasma concentrations of ACTH and corticosterone) and central concentrations of monoamines (norepinephrine, dopamine, and serotonin), by HPLC. Furthermore, will be performed the mapping of neuronal activation by immunoreactivity to c-fos protein, which allow us to identify the nature of the stimulus, through the activation of specific areas of the CNS, such as the nucleus of the solitary tract, parabrachial nucleus and locus coeruleus to physical stressors; and areas of the limbic system (amygdala, hippocampus) to psychological stressors. (AU)