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      Transcriptome Analysis Reveals Altered Expression of Memory and Neurotransmission Associated Genes in the REM Sleep Deprived Rat Brain

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          Abstract

          Sleep disorders are associated with cognitive impairment. Selective rapid eye movement sleep (REMS) deprivation (REMSD) alters several physiological processes and behaviors. By employing NGS platform we carried out transcriptomic analysis in brain samples of control rats and those exposed to REMSD. The expression of genes involved in chromatin assembly, methylation, learning, memory, regulation of synaptic transmission, neuronal plasticity and neurohypophysial hormone synthesis were altered. Increased transcription of BMP4, DBH and ATP1B2 genes after REMSD supports our earlier findings and hypothesis. Alteration in the transcripts encoding histone subtypes and important players in chromatin remodeling was observed. The mRNAs which transcribe neurotransmitters such as OXT, AVP, PMCH and LNPEP and two small non-coding RNAs, namely RMRP and BC1 were down regulated. At least some of these changes are likely to regulate REMS and may participate in the consequences of REMS loss. Thus, the findings of this study have identified key epigenetic regulators and neuronal plasticity genes associated to REMS and its loss. This analysis provides a background and opens up avenues for unraveling their specific roles in the complex behavioral network particularly in relation to sustained REMS-loss associated changes.

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          Most cited references69

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          Sleep and the price of plasticity: from synaptic and cellular homeostasis to memory consolidation and integration.

          Sleep is universal, tightly regulated, and its loss impairs cognition. But why does the brain need to disconnect from the environment for hours every day? The synaptic homeostasis hypothesis (SHY) proposes that sleep is the price the brain pays for plasticity. During a waking episode, learning statistical regularities about the current environment requires strengthening connections throughout the brain. This increases cellular needs for energy and supplies, decreases signal-to-noise ratios, and saturates learning. During sleep, spontaneous activity renormalizes net synaptic strength and restores cellular homeostasis. Activity-dependent down-selection of synapses can also explain the benefits of sleep on memory acquisition, consolidation, and integration. This happens through the offline, comprehensive sampling of statistical regularities incorporated in neuronal circuits over a lifetime. This Perspective considers the rationale and evidence for SHY and points to open issues related to sleep and plasticity. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Glutamate receptor function in learning and memory.

            G RIEDEL (2003)
            The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.
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              Extensive and divergent effects of sleep and wakefulness on brain gene expression.

              Sleep is present in all species where it has been studied, but its functions remain unknown. To investigate what benefits sleep may bring at the cellular level, we profiled gene expression in awake and sleeping rats by using high-density microarrays. We find that approximately 10% of the transcripts in the cerebral cortex change their expression between day and night and demonstrate that half of them are modulated by sleep and wakefulness independent of time of day. We also show that molecular correlates of sleep are found in the cerebellum, a structure not known for generating sleep rhythms. Finally, we show that different functional categories of genes are selectively associated with sleep and wakefulness. The approximately 100 known genes whose expression increases during sleep provide molecular support for the proposed involvement of sleep in protein synthesis and neural plasticity and point to a novel role for sleep in membrane trafficking and maintenance.
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                Author and article information

                Contributors
                Journal
                Front Mol Neurosci
                Front Mol Neurosci
                Front. Mol. Neurosci.
                Frontiers in Molecular Neuroscience
                Frontiers Media S.A.
                1662-5099
                17 March 2017
                2017
                : 10
                : 67
                Affiliations
                [1] 1Molecular Biology Research Laboratory, Center of Advanced Studies, Department of Zoology, Savitribai Phule Pune University Pune, India
                [2] 2School of Life Sciences, Jawaharlal Nehru University New Delhi, India
                [3] 3Bioinformatics Center, Savitribai Phule Pune University Pune, India
                Author notes

                Edited by: Detlev Boison, Legacy Health, USA

                Reviewed by: David Ruskin, Trinity College, USA; Barbara A. Sorg, Washington State University, USA

                *Correspondence: Deepti D. Deobagkar, deepti.deobagkar@ 123456gmail.com Birendra N. Mallick, remsbnm@ 123456yahoo.com
                Article
                10.3389/fnmol.2017.00067
                5355427
                28367113
                ca55095e-69d2-44a0-a273-e2a8024e2ae0
                Copyright © 2017 Narwade, Mallick and Deobagkar.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 December 2016
                : 28 February 2017
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 75, Pages: 13, Words: 0
                Funding
                Funded by: Indian Council of Medical Research 10.13039/501100001411
                Funded by: University Grants Commission 10.13039/501100001501
                Funded by: Department of Science and Technology, Ministry of Science and Technology 10.13039/501100001409
                Funded by: Department of Biotechnology, Ministry of Science and Technology 10.13039/501100001407
                Categories
                Neuroscience
                Original Research

                Neurosciences
                rem sleep deprivation,transcriptome,brain excitability,epigenetics,histone code,memory consolidation,neurotransmitter

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