Hippocampal CA1 Transcriptional Profile of Sleep Deprivation: Relation to Aging and Stress

Abstract

Background Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. Methodology/Principal Findings F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES), and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD -aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. Conclusions/Significance We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter effects of SD in young subjects.

The impact of sleep loss on hippocampal function

“…These widespread changes in hippocampal gene expression were reversed with 2.5 h of recovery sleep following sleep deprivation . Longer periods of sleep deprivation have also been examined with regard to gene expression in the hippocampus using microarray analysis to explore the relationship between age, stress, depression, and sleep disruption (Conti et al 2007;Porter et al 2012). In these studies, selective changes in genes related to presynaptic machinery and synaptic plasticity were identified.…”

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

“…These treatments were used to mimic stress effects and several studies reported the effects of the acute and chronic stresses modified differently the hippocampus transcriptome (Li et al, 2013; Stankiewicz et al, 2015). Furthermore, the nature of the stressor is also crucial (Porter et al, 2012; Li et al, 2013; Suri et al, 2014; Stankiewicz et al, 2015). Similarly to stress, modifications of living conditions, as well as long-term mild or intense exercise, can modulate the hippocampus transcriptome (Inoue et al, 2015).…”

Comparative transcriptome analysis of the hippocampus from sleep-deprived and Alzheimer’s disease mice

“…A recent study reports sleep deprivation disrupts hippocampal function and synaptic plasticity, a neural correlate of memory (Prince et al, 2014). It is well-known that sleep deprivation impairs memory, and hippocampus-dependent memory consolidation is particularly sensitive to sleep loss (Porter et al, 2012). The consolidation of memories includes synaptic consolidation and systems consolidation, both of which can be regulated by sleep deprivation (Havekes and Abel, 2017).…”