Perspective – ultrastructural analyses reflect the effects of sleep and sleep loss on neuronal cell biology

Abstract

Recent electron microscopic analyses of neurons in the Drosophila and rodent brain demonstrate that acute or chronic sleep loss can alter the structures of various organelles, including mitochondria, nucleus, and Golgi apparatus. Here, we discuss these findings in the context of biochemical findings from the sleep deprived brain, to clarify how these morphological changes may related to altered organelle function. We discuss how, taken together, the available data suggest that sleep loss (particularly chronic sleep loss) disrupts such fundamental cellular processes as transcription, translation, intracellular transport, and metabolism. A better understanding of these effects will have broad implications for understanding the biological importance of sleep, and the relationship of sleep loss to neuropathology.

Sleep-dependent engram reactivation during hippocampal memory consolidation is associated with subregion-specific biosynthetic changes

“…S7a ). This suggests strong and opposing effects of SD on mitochondrial vs. non-mitochondrial biogenesis, and supports recent work suggesting effects of SD on mitochondrial structure and function in neurons (35). In contrast to pathways identified in superior blade, inferior blade SD-altered transcripts overrepresented retrograde endocannabinoid signaling (KEGG: 04723; p adj = 0.042) and oxytocin signaling (KEGG: 04921; p adj = 0.084) pathway components.…”

“…Given this diversity – with SD effects on transcripts and proteins varying with cell compartment, type, and structure, it is plausible that our present findings could by biased due to technical aspects of our spatial profiling strategy. For example, because only the cell body layers are profiled in DG, CA3, and CA1, it is likely that transcripts which are efficiently transported out of the soma (i.e., into dendrites and axons) are undersampled using our technique (12, 35)(52, 53). In addition, we cannot discriminate between transcript changes occurring within the principal (i.e., pyramidal or granule) cell bodies, those occurring in presynaptic terminals of other excitatory, inhibitory, or neuromodulatory neurons which terminate in those layers, and those occurring in microglia, astrocytes or oligodendrocytes.…”

Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism

“…Sleep deprivation alters mitochondrial morphology, gene expression and oxidative phosphorylation activity in mice and humans. 20 , 21 , 22 , 23 , 24 , 25 , 26 Hence, we studied mitochondrial structure by transmission electron microscopy (TEM) imaging and quantified the mRNA expression and protein levels of genes associated with mitochondrial functions in all experimental mouse hearts. TEM ultrastructure analysis of both NTg-NSF and SF mouse heart tissue sections showed no significant alterations in the mitochondrial structure of sarcomere alignments ( Figures 4 A and 4B).…”

“…Sleep deprivation affects mitochondrial functions in various models. 20 , 21 , 22 , 23 , 24 , 25 In clinical setup, OSA patients display severe mitochondrial structure damage and increased mtDNA copy numbers. 46 , 47 In line with this evidence, we observed mitochondrial damage with significantly reduced Vdac1 (an outer mitochondrial membrane protein) levels and an increased CKmito levels in Tg-SF mouse heart tissues.…”

Dreaming reflects neural resynchronization after sleep-dependent neuroplastic adaptations.

“…These repair and modification processes are energy intensive and will conflict with the high energy demands of neural functioning that occur during wakefulness. Thus, sleep deprivation, sleep apnea, and insomnia, where the wake state is prolonged (and repair impaired), aggravate oxidative stress, neuroinflammation, neurodegeneration, and apoptosis (Besedovsky et al, 2019; Mahalakshmi et al, 2022; Suresh et al, 2021; Villafuerte et al, 2015; Wang & Aton, 2022), and degrades effective cognitive and immune function while sleep is restorative (e.g., Besedovsky et al, 2019; Klinzing et al, 2019; K. T. Li et al, 2022; Raven et al, 2019; Wunderlin et al, 2021).…”