Somatic genetics analysis of sleep in adult mice

2021 ◽  
Author(s):  
Qinghua Liu ◽  
Fengchao Wang ◽  
Guodong Wang ◽  
Qi Li ◽  
Junjie Xu ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Adult Brain ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Genetic Crosses ◽  
Adult Mice ◽  
Sleep Screening ◽  
Electroencephalogram Eeg

The molecular mechanisms of mammalian sleep regulation remain largely unknown. Classical forward and reverse mouse genetic approaches require germline mutations and, thus, are unwieldy to study the sleep functions of essential genes or redundant pathways. It is also costly and time-consuming to conduct large-scale electroencephalogram (EEG)/electromyogram (EMG)-based mouse sleep screening due to lengthy genetic crosses and labor-intensive surgeries. Here, we develop a highly efficient adult brain chimeric (ABC) expression/knockout (KO) platform and a highly accurate AI-augmented SleepV (video) system for high-througphut somatic genetics analysis of sleep in adult mice. This ABC platform involves intravenous administration of adeno-associated viruses (AAV) that bypass the blood brain barrier and transduce the majority of adult brain neurons. Constitutive or inducible ABC-expression of CREB and CRTC1 reduces both quantity and quality of non-rapid-eye-movement sleep (NREMS), whereas ABC-KO of CREB by AAV-mediated Cre/loxP recombination increases daily NREMS amount. Moreover, ABC-KO of exon 13 of Sik3 by AAV-Cre injection of Sik3-E13flox/flox adult mice phenocopies Sleepy (Sik3Slp/Slp) mice, which carry a germline splicing mutation resulting in skipping of exon 13 of Sik3. While both long and short isoforms of SLP kinase contribute to, ABC-KO of Slp allele by CRISPR/Cas9 rescues the hypersomnia of Sik3Slp/+ mice. Double ABC-KO of orexin/hypocretin receptors by CRISPR/Cas9 results in chocolate-induced narcolepsy episodes. We envision that these somatic genetics approaches should facilitate efficient and sophisticated studies of many brain-related cellular, physiological and behavioral processes in adult mice without genetic crosses.

scholarly journals Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ettore Tiraboschi ◽  
Ramon Guirado ◽  
Dario Greco ◽  
Petri Auvinen ◽  
Jose Fernando Maya-Vetencourt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Cortex ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Gene Expression Patterns ◽  
Postnatal Life ◽  
Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

scholarly journals In Vivo Imaging of Cerebral Microvascular Plasticity from Birth to Death

2012 ◽  
Vol 33 (1) ◽  
pp. 146-156 ◽  
Author(s):  
Roa Harb ◽  
Christina Whiteus ◽  
Catarina Freitas ◽  
Jaime Grutzendler
Keyword(s):  
Large Scale ◽  
Time Lapse ◽  
Confocal Imaging ◽  
Adult Brain ◽  
Vessel Formation ◽  
Adult Mice ◽  
Age Related ◽  
Vascular Stability

Cerebral function and viability are critically dependent on efficient delivery of oxygen and glucose through the microvasculature. Here, we studied individual microvessels in the intact brain using high-resolution confocal imaging and long-term time-lapse two-photon microscopy across the lifetime of a mouse. In the first postnatal month, we found large-scale sprouting but to our surprise the majority of sprouts underwent pruning and only a small fraction became perfused capillaries. After the first month, microvessel formation and elimination decreased and the net number of vessels stabilized. Although vascular stability was the hallmark of the adult brain, some vessel formation and elimination continued throughout life. In young adult mice, vessel formation was markedly increased after exposure to hypoxia; however, upon return to normoxia, no vessel elimination was observed, suggesting that new vessels constitute a long-term adaptive response to metabolic challenges. This plasticity was markedly reduced in older adults and aging where hypoxia-induced angiogenesis was absent. Our study describes, for the first time in vivo patterns of cerebral microvascular remodeling throughout life. Disruption of the observed balance between baseline turnover and vascular stability may underlie a variety of developmental and age-related degenerative neurological disorders.

Dynamics of the sleep EEG after an early evening nap: experimental data and simulations

1996 ◽  
Vol 271 (3) ◽  
pp. R501-R510 ◽  
Author(s):  
E. Werth ◽  
D. J. Dijk ◽  
P. Achermann ◽  
A. A. Borbely
Keyword(s):  
Power Density ◽  
Time Course ◽  
Sleep Eeg ◽  
Rapid Eye Movement Sleep ◽  
Theta Band ◽  
Sleep Regulation ◽  
Homeostatic Model ◽  
Nighttime Sleep ◽  
Electroencephalogram Eeg ◽  
Homeostatic Mechanisms

Increasing sleep pressure is associated with highly predictable changes in the dynamics of the sleep electroencephalogram (EEG). To investigate whether the effects of reduced sleep pressure also can be accounted for by homeostatic mechanisms, nighttime sleep following an evening nap was recorded in healthy young men. In comparison with the baseline night, sleep latency in the postnap night was prolonged, rapid eye movement sleep (REMS) latency was reduced, and EEG power density in non-REMS was decreased in the delta and theta band. The buildup of both EEG slow-wave activity (SWA; power density in the 0.75-to 4.5-Hz range) and spindle frequency activity (SFA; power density in the 12.25-to 15.0-Hz range) in non-REMS episodes was diminished (SWA: episodes 1-3; SFA: episode 1). The typical declining trend of SWA over consecutive non-REM sleep episodes was attenuated. The time course of SWA could be closely simulated with a homeostatic model of sleep regulation, although some discrepancies in level and buildup of SWA were apparent. We conclude that homeostatic mechanisms can largely account for the dynamics of the sleep EEG under conditions of reduced sleep pressure.

scholarly journals Estrogen and neuroprotection: from clinical observations to molecular mechanisms

2002 ◽  
Vol 4 (2) ◽  
pp. 149-161 ◽  
Keyword(s):  
Molecular Mechanisms ◽  
Science Studies ◽  
Adult Brain ◽  
Health Concern ◽  
Past Century ◽  
Clinical Observations ◽  
Protective Actions ◽  
Increased Risk ◽  
The Impact

We now appreciate that estrogen is a pleiotropic gonadal steroid that exerts profound effects on the plasticity and cell survival of the adult brain. Over the past century, the life span of women has increased, but the age of the menopause remains constant. This means that women may now live over one third of their lives in a hypoestrogenic, postmenopausal state. The impact of prolonged hypoestrogenicity on the brain is now a critical health concern as we realize that these women may suffer an increased risk of cognitive dysfunction and neurodegeneration due to a variety of diseases. Accumulating evidence from both clinical and basic science studies indicates that estrogen exerts critical protective actions against neurodegenerative conditions such as Alzheimer's disease and stroke. Here, we review the discoveries that comprise our current understanding of estrogen action against neurodegeneration. These findings carry far-reaching possibilities for improving the quality of life in our aging population.

Sleep regulation in rats during early development

1990 ◽  
Vol 258 (3) ◽  
pp. R634-R644 ◽  
Author(s):  
P. Alfoldi ◽  
I. Tobler ◽  
A. A. Borbely
Keyword(s):  
High Frequency ◽  
Dark Period ◽  
Power Spectra ◽  
Light Period ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Age Related ◽  
High Frequency Activity ◽  
Freely Moving ◽  
Electroencephalogram Eeg

Sleep states and power spectra of the electroencephalogram (EEG) were determined in freely moving young rats. Recordings during 24 h were obtained from the same animals at three different ages. Already at the age of 23 days waking predominated in the 12-h dark period. Rapid-eye-movement sleep (REMS) declined between the age of 23 and 40 days. Its 24-h maximum was situated in the dark period at 23 and 29 days of age and in the light period at 40 days. Slow-wave activity (SWA; 0.75-4.0 Hz) of the non-REMS (NREMS) EEG showed marked age-related changes: a declining trend in the 12-h light period was absent at 23 days, moderate at 29 days, and prominent at 40 days. At 23 days, SWA progressively declined within ultradian sleep episodes and at 24 days was massively increased after 2-h sleep deprivation (SD). At the age of 30 days, 6-h SD induced much smaller changes. The distinct 24-h pattern of high-frequency activity (10.25-25.0 Hz) was present at all ages and may represent an EEG correlate of a circadian process. We conclude that homeostatic mechanisms regulating NREMS intensity are already operative a few days after weaning.

Sleep of transgenic mice producing excess rat growth hormone

2002 ◽  
Vol 282 (1) ◽  
pp. R70-R76 ◽  
Author(s):  
I. Hajdu ◽  
F. Obal ◽  
J. Fang ◽  
J. M. Krueger ◽  
C. D. Rollo
Keyword(s):  
Growth Hormone ◽  
Transgenic Mice ◽  
Eye Movement ◽  
Hormonal Changes ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Rat Growth ◽  
Electroencephalogram Eeg

The effects of chronic excess of growth hormone (GH) on sleep-wake activity was determined in giant transgenic mice in which the metallothionein-1 promoter stimulates the expression of rat GH (MT-rGH mice) and in their normal littermates. In the MT-rGH mice, the time spent in spontaneous non-rapid eye movement sleep (NREMS) was enhanced moderately, and rapid eye movement sleep (REMS) time increased greatly during the light period. After a 12-h sleep deprivation, the MT-rGH mice continued to sleep more than the normal mice, but there were no differences in the increments in NREMS, REMS, and electroencephalogram (EEG) slow-wave activity (SWA) during NREMS between the two groups. Injection of the somatostatin analog octreotide elicited a prompt sleep suppression followed by increases in SWA during NREMS in normal mice. These changes were attenuated in the MT-rGH mice. The decreased responsiveness to octreotide is explained by a chronic suppression of hypothalamic GH-releasing hormone in the MT-rGH mice. Enhancements in spontaneous REMS are attributed to the REMS-promoting activity of GH. The increases in spontaneous NREMS are, however, not consistent with our current understanding of the role of somatotropic hormones in sleep regulation. Metabolic, neurotransmitter, or hormonal changes associated with chronic GH excess may indirectly influence sleep.

Assessment of quality of life in patients with the effects of transient ischemic stroke

2016 ◽  
pp. 37-39
Author(s):  
A. Babirad
Keyword(s):  
Quality Of Life ◽  
Ischemic Stroke ◽  
Large Scale ◽  
Cerebrovascular Diseases ◽  
Control Measures ◽  
Sociological Research ◽  
Cerebrovascular Events ◽  
Sf 36 ◽  
Angioplasty And Stenting

Cerebrovascular diseases are a problem of the world today, and according to the forecast, the problem of the near future arises. The main risk factors for the development of ischemic disorders of the cerebral circulation include oblique and aging, arterial hypertension, smoking, diabetes mellitus and heart disease. An effective strategy for the prevention of cerebrovascular events is based on the implementation of large-scale risk control measures, including the use of antiagregant and anticoagulant therapy, invasive interventions such as atheromectomy, angioplasty and stenting. In this connection, the efforts of neurologists, cardiologists, angiosurgery, endocrinologists and other specialists are the basis for achieving an acceptable clinical outcome. A review of the SF-36 method for assessing the quality of life in patients with the effects of transient ischemic stroke is presented. The assessment of quality of life is recognized in world medical practice and research, an indicator that is also used to assess the quality of the health system and in general sociological research.

Model and Method for Contributor’s Quality Assessment in Community Image Tagging Systems

2018 ◽  
pp. 45-51
Author(s):  
A. V. Ponomarev
Keyword(s):  
Large Scale ◽  
Wide Spectrum ◽  
Preference Relation ◽  
Pairwise Comparison ◽  
Ground Truth ◽  
Comparison Method ◽  
Characteristic Matrix ◽  
Image Tagging ◽  
Proposed Model

Introduction: Large-scale human-computer systems involving people of various skills and motivation into the information processing process are currently used in a wide spectrum of applications. An acute problem in such systems is assessing the expected quality of each contributor; for example, in order to penalize incompetent or inaccurate ones and to promote diligent ones.Purpose: To develop a method of assessing the expected contributor’s quality in community tagging systems. This method should only use generally unreliable and incomplete information provided by contributors (with ground truth tags unknown).Results:A mathematical model is proposed for community image tagging (including the model of a contributor), along with a method of assessing the expected contributor’s quality. The method is based on comparing tag sets provided by different contributors for the same images, being a modification of pairwise comparison method with preference relation replaced by a special domination characteristic. Expected contributors’ quality is evaluated as a positive eigenvector of a pairwise domination characteristic matrix. Community tagging simulation has confirmed that the proposed method allows you to adequately estimate the expected quality of community tagging system contributors (provided that the contributors' behavior fits the proposed model).Practical relevance: The obtained results can be used in the development of systems based on coordinated efforts of community (primarily, community tagging systems). 

Translation and Validation of the Thai Version of the Wisconsin Quality of Life Questionnaire (TH WISQoL) for Kidney Stone Patients

2020 ◽  
Vol 103 (11) ◽  
pp. 1194-1199
Keyword(s):  
Quality Of Life ◽  
Internal Consistency ◽  
Kidney Stone ◽  
Convergent Validity ◽  
Large Scale ◽  
Short Form ◽  
Outcome Measurement ◽  
Life Questionnaire ◽  
Sf 36

Objective: To develop and validate a Thai version of the Wisconsin Quality of Life (TH WISQoL) Questionnaire. Materials and Methods: The authors developed the TH WISQoL Questionnaire based on a standard multi-step process. Subsequently, the authors recruited patients with kidney stone and requested them to complete the TH WISQoL and a validated Thai version of the 36-Item Short Form Survey (TH SF-36). The authors calculated the internal consistency and interdomain correlation of TH WISQoL and compared the convergent validity between the two instruments. Results: Thirty kidney stone patients completed the TH WISQoL and the TH SF-36. The TH WISQoL showed acceptable internal consistency for all domains (Cronbach’s alpha 0.768 to 0.909). Interdomain correlation was high for most domains (r=0.698 to 0.779), except for the correlation between Vitality and Disease domains, which showed a moderate correlation (r=0.575). For convergent validity, TH WISQoL demonstrated a good overall correlation to TH SF-36, (r=0.796, p<0.05). Conclusion: The TH WISQoL is valid and reliable for evaluating the quality of life of Thai patients with kidney stone. A further large-scale multi-center study is warranted to confirm its applicability in Thailand. Keywords: Quality of life, Kidney stone, Validation, Outcome measurement

Evaluating Qualitative Research

2017 ◽  
Author(s):  
Jeasik Cho
Keyword(s):  
Qualitative Research ◽  
Large Scale ◽  
Academic Research ◽  
Research Community ◽  
Assessment Tools ◽  
Journal Articles ◽  
Journal Editors ◽  
The Past ◽  
Grant Proposals

This book provides the qualitative research community with some insight on how to evaluate the quality of qualitative research. This topic has gained little attention during the past few decades. We, qualitative researchers, read journal articles, serve on masters’ and doctoral committees, and also make decisions on whether conference proposals, manuscripts, or large-scale grant proposals should be accepted or rejected. It is assumed that various perspectives or criteria, depending on various paradigms, theories, or fields of discipline, have been used in assessing the quality of qualitative research. Nonetheless, until now, no textbook has been specifically devoted to exploring theories, practices, and reflections associated with the evaluation of qualitative research. This book constructs a typology of evaluating qualitative research, examines actual information from websites and qualitative journal editors, and reflects on some challenges that are currently encountered by the qualitative research community. Many different kinds of journals’ review guidelines and available assessment tools are collected and analyzed. Consequently, core criteria that stand out among these evaluation tools are presented. Readers are invited to join the author to confidently proclaim: “Fortunately, there are commonly agreed, bold standards for evaluating the goodness of qualitative research in the academic research community. These standards are a part of what is generally called ‘scientific research.’ ”

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