Impact of REM sleep deprivation during the acquisition phase on learning and memory performance, neurotrophic and oxidative stress markers in male rats

Abstract

During adolescence, the brain is particularly vulnerable to sleep disruption, which may lead to long‑term memory deficits and emotional dysregulation. This study investigated the impact of REM sleep deprivation (REM‑SD), applied specifically during the acquisition phase of learning, on spatial memory, anxiety‑like behavior, and hippocampal neurotrophic and oxidative status in adolescent rats. Male adolescent Wistar Albino rats were subjected to a REM‑SD protocol using the modified multiple platform method (MMPM), integrated directly into the training phase of the Morris water maze (MWM). Animals were divided into three groups: Control, Pedestal Control, and REM‑SD. Anxiety‑like behavior was assessed using the open field (OFT) and elevated plus maze (EPM) tests. Corticosterone levels and hippocampal levels of nerve growth factor (NGF), brain‑derived neurotrophic factor (BDNF), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), and malondialdehyde (MDA) were analyzed by ELISA. REM‑SD during the acquisition phase significantly impaired memory performance in the MWM probe trial. In the OFT test, REM‑SD rats exhibited increased anxiety‑like behavior, reflected by reduced time spent in the center zone, whereas the EPM demonstrated increased open‑arm duration. These behavioral alterations were accompanied by significantly elevated corticosterone levels. REM‑SD was associated with reduced hippocampal antioxidant status (decreased TAS and SOD), decreased NGF levels, and increased oxidative status (TOS). Our findings demonstrate that exposure to the MMPM, together with REM sleep disruption and associated stress‑related physiological responses, was accompanied by alterations in memory performance, corticosterone levels, oxidative balance, and neurotrophic markers. The observed behavioral changes, including alterations during late acquisition and impaired probe trial performance, may reflect combined effects on learning‑ and memory‑related processes.