Sleep deprivation induce morphology changes in the hippocampus and prefrontal cortex in young and old rats

Abstract

Introduction During normal aging several changes in sleep/wake patterns are observed, which include frequent awakenings during sleep and increased daytime naps, among others. Likewise, aging has also been associated with a deterioration of cognitive function, learning and memory, although widespread loss of nerve cells does not occur, the most of age-related structural changes observed in nerve cells are modifications in dendrites, dendritic spines or even axons. Evidence accumulated over the last years indicates that these functional changes observed during sleep loss, aging, or both could be due to modifications in synaptic connectivity and intracellular signaling; for example, excitatory synaptic transmission at the hippocampal CA1 region is affected by sleep deprivation; in the locus coeruleus (involved in both arousal system and cognitive performance) the number of neurons projecting to areas such as the cortex and the hippocampus declines with age. Therefore, it has been hypothesized that sleep deprivation may compromise neurophysiological and behavioral events; however, relatively few studies have investigated links between sleep loss and structural changes in neurons and, despite the seemingly similar effects of age and sleep deprivation on cognition and the prevalence of sleep changes with age, little is known about the impact of sleep loss on cellular morphology in aging neurons. For that reasons, the aim of this study was to evaluate the effects of total sleep deprivation on neuronal morphology in the hippocampus and prefrontal cortex of both young and aged animals. Materials and methods A total of 28 male Wistar rats (14 “young-adult” rats, 3–4 months old; 14 “aged rats”, 22–23 months old; 7 for control and 7 for sleep deprivation for each age) were used in this study. Total sleep deprivation was carried out in both experimental groups (young-adult and aged, n = 7 per group) by gentle handling: once sleep-behaviour was observed or low amplitude waves first appear in sleep recording, rats were softly touched in their tails, whiskers or handling them to prevent falling asleep during 24 h. Immediately after sleep deprivation finished, animals were deeply anesthetized with sodium pentobarbital (75 mg/kg, i.p.) and then perfused intracardially with 0.9% saline solution. Brains were removed and stained by modified Golgi-Cox method. Pyramidal neurons from layer 3 of prefrontal cortex and hippocampus (CA1 area) were selected for study. Five neurons from each region of each brain hemisphere per animal were drawn using a camera lucida. Basal dendrites, including all branches, were reconstructed for each neuron and their dendritic tracings were quantified by Sholl analysis. Results Results showed that total dendritic length of prefrontal cortex and hippocampus was not affected either age or after 24 h of sleep deprivation compared to their corresponding control group. However, after 24 h of sleep deprivation (SD) aged animals had an increase in spine density in prefrontal cortex but not in hippocampus. Conclusion Sleep deprivation could be considered a factor that induces neuronal plasticity, which may depend on age. Acknowledgement This study was supported by CONACYT grant 133178.