Dataset Information

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

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.

SUBMITTER: Narwade SC

PROVIDER: S-EPMC5355427 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Narwade Santosh C SC Mallick Birendra N BN Deobagkar Deepti D DD

Frontiers in molecular neuroscience 20170317

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. Inc ...[more]

PMID: 28367113

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Project description:Obstructive sleep apnea (OSA) is characterized by the frequent presence of neuro-cognitive impairment. Recent studies associate cognitive dysfunction with altered resting-state brain connectivity between key nodes of the executive and default-mode networks, two anti-correlated functional networks whose strength of activation increases or decreases with cognitive activity, respectively. To date no study has investigated a relationship between cognitive impairment in OSA and brain connectivity during an active working-memory challenge. We thus investigated the effect of OSA on working-memory performance and underlying brain connectivity. OSA patients and matched healthy controls underwent functional magnetic resonance imaging (fMRI) scanning while performing a 2-back working-memory task. Standard fMRI analyses highlighted the brain regions activated at increasing levels of working-memory load, which were used as seeds in connectivity analyses. The latter were based on a multiregional Psycho-Physiological-Interaction (PPI) approach, to unveil group differences in effective connectivity underlying working-memory performance. Compared with controls, in OSA patients normal working-memory performance reflected in: a) reduced interhemispheric effective connectivity between the frontal "executive" nodes of the working-memory network, and b) increased right-hemispheric connectivity among regions mediating the "salience-based" switch from the default resting-state mode to the effortful cognitive activity associated with the executive network. The strength of such connections was correlated, at increasing task-demands, with executive (Stroop test) and memory (Digit Span test) performance in neuro-cognitive evaluations. The analysis of effective connectivity changes during a working-memory challenge provides a complementary window, compared with resting-state studies, on the mechanisms supporting preserved performance despite functional and structural brain modifications in OSA.

Project description:Background Social anxiety disorder (SAD) is characterized by a significant amount of fear when confronted to social situations. Exposure therapy, which is based on fear extinction, does not often lead to full remission. Here, based on evidence showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning in SAD. Methods Forty-eight subjects with SAD were randomly assigned to two groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N = 24), a sound was paired to the positive feedback phase of therapy (i.e., approval of their performance), which represented the memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages and administered the sound during REM sleep. Participants' anxiety level was assessed using measures of parasympathetic (root mean square of successive differences between normal heartbeats, RMSSD) and sympathetic (non-specific skin conductance responses, ns-SCRs) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their talks before (T1) and after (T2) one full-night's sleep and after 1 week at home (T3). Participants also filled in a dream diary. Results We observed an effect of time on subjective measures of anxiety (SUDS). We did not find any difference in the anxiety levels of the two groups after 1 week of TMR at home. Importantly, the longer the total duration of REM sleep and the more stimulations the TMR group had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with ns-SCRs and SUDS at T3 in the TMR group. Conclusion TMR during REM sleep did not significantly modulate the beneficial effect of therapy on subjective anxiety. Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotions in dreams and waking stress levels in these patients.

Dataset Information

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

Publications

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

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