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Chronic REM sleep restriction during adolescence as a risk factor for attention deficits and changes in oxidative stress markers in SHR rats

Grant number: 22/07832-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2022
Effective date (End): April 30, 2026
Field of knowledge:Humanities - Psychology - Physiological Psychology
Principal Investigator:Regina Cláudia Barbosa da Silva
Grantee:Lucas de Santana Cardoso Thomaz
Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

During adolescence, sleep is altered to adapt to the changes characteristic of this period, especially those related to neurodevelopment, leading to an increase in the amount of sleep required during this period. However, adolescents have been sleeping less than necessary and chronic sleep restriction is related to neurobiological changes and impairments in cognitive capacity, in addition to being implicated in the etiology of several neurological and neurodegenerative disorders such as Schizophrenia. Patients with Schizophrenia report sleep disturbances and also have cognitive deficits that most commonly arise during adolescence. The aim of the present study will be to investigate the effects of chronic REM sleep restriction (RSREM/18 h daily) for 21 consecutive days (DPN32-DPN52) in SHR rats tested in adolescence (DPN 54) and adulthood (DPN120) for Prepulse Inhibition (PPI) response of the acoustic startle reflex and oxidative stress markers in the prefrontal cortex, striatum and hippocampus, regions involved in the pathophysiology of Schizophrenia. Additionally, the effects of i.p. of the antipsychotic clozapine (CLZ) 30 min before the PPI test in preventing possible deficits in this response. Will be used 24 Wistar rats and 120 male adolescent SHR distributed in different experiments: Pilot Experiment (Wistar/CTL = 24; SHR = 24); Experiment 1 (SHR/CTL = 12; SHR/RSREM = 12; DPN test 54); Experiment 2 (SHR/CTL = 12; SHR/RSREM = 12; DPN test 120); Experiment 3 (SHR/RSREM+SAL = 12; SHR/RSREM + CLZ = 12; DPN test 54) and Experiment 4 (SHR/RSREM+SAL = 12;SHR/RSREM+ CLZ = 12; DPN test 120). The hypothesis is that deficits in the IPP response will be potentiated by the restriction of REM sleep in SHR rats, also producing alterations in measures of oxidative stress and that such deficits and alterations can be prevented by the acute administration of CLZ. (AU)

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