The short- and long-term proteomic effects of sleep deprivation on the cortical and thalamic synapses

Simor, Attila; Győrffy, Balázs; Gulyássy, Péter; Völgyi, Katalin; Tóth, Vilmos; Todorov, Mihail Ivilinov; Kis, Viktor; Borhegyi, Zsolt; Szabó, Z. G.; Janáky, Tamás; Drahos, László; Juhász, Gábor; Kékesi, Katalin A.

doi:10.1016/j.mcn.2017.01.002

Cited by 12 publications

(10 citation statements)

References 84 publications

(86 reference statements)

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“…At the level of brain structures and molecules, wakefulness is governed by neurons in the upper brainstem projecting to higher brain areas, and monoaminergic neurons and cholinergic neurons provide input to the thalamus, which plays an important role in the maintenance of wakefulness (Saper et al, 2010 ). An animal study showed widespread proteomic alterations in the thalamic synapses due to sleep deprivation (Simor et al, 2017 ). Similarly, patients, with lesions just limited to the thalamus, are usually in an awake state (Posner et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

Yan

Liu

Wang

et al. 2018

Front. Aging Neurosci.

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Background: Recently, there have been many reports about abnormalities regarding structural and functional brain connectivity of the patients with primary insomnia. However, the alterations in functional interaction between the left and right cerebral hemispheres have not been well understood. The resting-state fMRI approach, which reveals spontaneous neural fluctuations in blood-oxygen-level-dependent signals, offers a method to quantify functional interactions between the hemispheres directly.Methods: We compared interhemispheric functional connectivity (FC) between 26 patients with primary insomnia (48.85 ± 12.02 years) and 28 healthy controls (49.07 ± 11.81 years) using a voxel-mirrored homotopic connectivity (VMHC) method. The patients with primary insomnia and healthy controls were matched for age, gender, and education. Brain regions, which had significant differences in VMHC maps between the primary insomnia and healthy control groups, were defined as seed region of interests. A seed-based approach was further used to reveal significant differences of FC between the seeds and the whole contralateral hemisphere.Results: The patients with primary insomnia showed higher VMHC than healthy controls in the anterior cingulate cortex (ACC) bilaterally. The seed-based analyses demonstrated increased FC between the left ACC and right thalamus (and the right ACC and left orbitofrontal cortex) in patients with primary insomnia, revealing abnormal connectivity between the two cerebral hemispheres. The VMHC values in the ACC were positively correlated with the time to fall asleep and Self-Rating Depression Scale scores (SDS).Conclusions: The results demonstrate that there is abnormal interhemispheric resting-state FC in the brain regions of patients with primary insomnia, especially in the ACC. Our finding demonstrates valid evidence that the ACC is an area of interest in the neurobiology of primary insomnia.

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Section: Discussionmentioning

confidence: 99%

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

Yan

Liu

Wang

et al. 2018

Front. Aging Neurosci.

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“…A critical unresolved question is whether the levels of protein translated from sleep- and wake-regulated mRNAs are similarly altered by state. Changes in protein levels appear to track transcript level changes in some of the cases where it has been carefully investigated (Cirelli et al, 1996 ; Simor et al, 2017 ). However, state-dependent changes in protein synthesis (Ramm and Smith, 1990 ) may compensate for some changes in gene expression during SD.…”

Section: Part I: the Synaptic Homeostasis Hypothesismentioning

confidence: 99%

Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data

Puentes-Mestril

Aton

2017

Front. Neural Circuits

111

123

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Research findings over the past two decades have supported a link between sleep states and synaptic plasticity. Numerous mechanistic hypotheses have been put forth to explain this relationship. For example, multiple studies have shown structural alterations to synapses (including changes in synaptic volume, spine density, and receptor composition) indicative of synaptic weakening after a period of sleep. Direct measures of neuronal activity and synaptic strength support the idea that a period of sleep can reduce synaptic strength. This has led to the synaptic homeostasis hypothesis (SHY), which asserts that during slow wave sleep, synapses are downscaled throughout the brain to counteract net strengthening of network synapses during waking experience (e.g., during learning). However, neither the cellular mechanisms mediating these synaptic changes, nor the sleep-dependent activity changes driving those cellular events are well-defined. Here we discuss potential cellular and network dynamic mechanisms which could underlie reductions in synaptic strength during sleep. We also discuss recent findings demonstrating circuit-specific synaptic strengthening (rather than weakening) during sleep. Based on these data, we explore the hypothetical role of sleep-associated network activity patterns in driving synaptic strengthening. We propose an alternative to SHY—namely that depending on experience during prior wake, a variety of plasticity mechanisms may operate in the brain during sleep. We conclude that either synaptic strengthening or synaptic weakening can occur across sleep, depending on changes to specific neural circuits (such as gene expression and protein translation) induced by experiences in wake. Clarifying the mechanisms underlying these different forms of sleep-dependent plasticity will significantly advance our understanding of how sleep benefits various cognitive functions.

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“…However, it is also important to note that contaminations from other cellular organelles are not entirely excluded and present in a non-negligible extent in samples. At the same time, the applied synaptosome preparation is highly reproducible and its power in synaptosome-enrichment was validated several times 25,30,31 .…”

Section: Discussionmentioning

confidence: 99%

Chronic stepwise cerebral hypoperfusion differentially induces synaptic proteome changes in the frontal cortex, occipital cortex, and hippocampus in rats

Tukacs

Mittli

Győrffy

et al. 2020

Sci Rep

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During chronic cerebral hypoperfusion (CCH), the cerebral blood flow gradually decreases, leading to cognitive impairments and neurodegenerative disorders, such as vascular dementia. The reduced oxygenation, energy supply induced metabolic changes, and insufficient neuroplasticity could be reflected in the synaptic proteome. We performed stepwise bilateral common carotid occlusions on rats and studied the synaptic proteome changes of the hippocampus, occipital and frontal cortices. Samples were prepared and separated by 2-D DIGE and significantly altered protein spots were identified by HPLC–MS/MS. We revealed an outstanding amount of protein changes in the occipital cortex compared to the frontal cortex and the hippocampus with 94, 33, and 17 proteins, respectively. The high alterations in the occipital cortex are probably due to the hypoxia-induced retrograde degeneration of the primary visual cortex, which was demonstrated by electrophysiological experiments. Altered proteins have functions related to cytoskeletal organization and energy metabolism. As CCH could also be an important risk factor for Alzheimer’s disease (AD), we investigated whether our altered proteins overlap with AD protein databases. We revealed a significant amount of altered proteins associated with AD in the two neocortical areas, suggesting a prominent overlap with the AD pathomechanism.

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The short- and long-term proteomic effects of sleep deprivation on the cortical and thalamic synapses

Cited by 12 publications

References 84 publications

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

Abnormal Functional Connectivity of Anterior Cingulate Cortex in Patients With Primary Insomnia: A Resting-State Functional Magnetic Resonance Imaging Study

Linking Network Activity to Synaptic Plasticity during Sleep: Hypotheses and Recent Data

Chronic stepwise cerebral hypoperfusion differentially induces synaptic proteome changes in the frontal cortex, occipital cortex, and hippocampus in rats

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