RP5 Sleep Medicine and Chronobiology – Running Grants and Projects

The Czech Science Foundation

Psychoplastogenicity of Psilocybin – the Interplay of Serotonergic Mechanisms, Sleep-wake Cycle and Neuroplasticity on Memory Consolidation (20-25349S)
Investigator: doc. RNDr. Zdeňka Bendová, Ph.D.
Principle investigator: NIMH
Duration: 1.1.2020–31.12.2022
Total budget NIMH: 12 029 000 CZK
Abstract: Serotonergic psychedelic psilocybin is currently extensively studied as a so-called fast-acting antidepressant in the indication of pharmacoresistant depression. One of the most likely mechanisms leading to an antidepressant effect is the induction of synaptic plasticity. In depression cognitive deficits are a common symptom. Previously we have found that psilocin improves spatial memory consolidation in the rat. The aim of the project is therefore to evaluate the effect of 5-HT2A/C and 5-HT1A agonist psilocybin on the hippocampus-dependent memory consolidation in Morris water maze and novel object and place recognition tasks in relation to synaptic plasticity in the rat. In order to evaluate the effect of sleep and sleep deprivation, EEG / EMG and behavioural activity will be continuously recorded in animals via wireless implantable telemetry. Synaptic plasticity will be evaluated in 3D brain organoids derived from animals from cognitive experiments. The role of 5-HT2A/C and 5-HT1A receptors will be assessed using selective antagonists in both in vivo models and organoids.

 

Czech Health Research Council 

Gut Microbiome and Autoimmune Mechanisms in Patients with Central Hypersomnia 
(NU20-04-00088)
Investigator: MUDr. Jitka Bušková, Ph.D.
Principle investigator: Všeobecná fakultní nemocnice v Praze
Project partners: NIMH, Mikrobiologický ústav AV ČR
Duration: 1.5.2020–31.12.2023
Total budget: 13 999 000 Kč
Total budget NIMH: 1 807 000 Kč
Abstract: Narcolepsy type 1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH)
have as a main symptom central hypersomnia (CH). The etiopathophysiology of NT1 is related to the hypocretin deficiency of autoimmune origin. The etiopathophysiology of NT2 and IH is unknown. There are doubts on the independence of NT2 and IH and their long-term course. The gut microbiota has an impact on brain functions and behavior either directly by mediators’ production or indirectly via autoantibodies against selected neurons. This evokes the hypothesis that microbiota has a role in etiopathophysiology of diseases with CH and may modify actual intensity of hypersomnia itself. Patients with CH and healthy controls will be clinically examined (including the long-term evolution of NT2 and IH). Their stools will be genetically analyzed in attempt to define the microbiome of the gut microbiota. The autoantibodies will be searched in their blood. The results will be mutually correlated. This research may elucidate the pathophysiology of CH disorders as well as may help to counselling the patients and fina
Primary scientific aims: 1. To analyze the composition of the intestinal microbiome in patients with central hypersomnia and to compare it to healthy individuals. 2. To compare the composition of the gut microbiome in NT1, NT2, IH, and healthy controls. 3. To detect potential changes in intestinal barrier functions in patients with central hypersomnia. 4. To determine levels of autoantibodies against hypocretin in the serum of patients with central hypersomnia and in healthy subjects and to detect other possible autoantibodies against neuronal antigens in the serum of patients with central hypersomnia. 5. To correlate the changes found in gut microbiome composition, gut barrier function and autoantibody levels with clinical findings in patients (day-time sleep parameters, night sleep quality, co-morbidity such as depression, REM sleep muscle atonia disturbances, restless leg syndrome, sleep apnea, treatment etc.), and with parameters of biological samples obtained earlier in the diagnosis of disease (blood, HLA DQB1*0602 positivity and cerebrospinal fluid hypocretin level).
Secondary scientific aims: 1. To describe retrospectively the long-term evolution of NT2 and IH and to describe the clinical status of NT2 and IH in the elderly. 2. To analyze the influence of microbiota and eating habits on efficacy of standard pharmacological treatments. 3. Validation of Narcolepsy severity scale and Idiopathic hypersomnia severity scale in the Czech language. 4. Further participation of both
clinical departments in EU-NN scientific program (http://eu-nn.com/) (database etc.). 

 

The Technology Agency of The Czech Republic

Stable and mobile devices to support circadian synchronization, treatment and prevention of mental disorders through full-spectrum light phototherapy (FW02020025)
Investigator: PhDr. Jana Kopřivová, Ph.D.
Principle investigator: Spectrasol, s.r.o.
Project partners: National Institute of Mental Health; Czech Technical University, University Centre for Energy Efficient Buildings
Duration: 1.7.2020–30.9.2023
Total budget: 15 602 098 CZK
Total budget NIMH: 5 496 873 CZK
Abstract:
The goal of the project is to design and produce a series of phototherapeutic devices using a unique balanced-spectrum LED light source, and to verify their effects. The proposed devices are intended to prevent or support treatment of mood disorders, such as seasonal affective disorder (SAD), bipolar disorder, postnatal depression, and many other applications in psychiatric care. Device will be developed in 3 variation of the size and use, ranging from a self-standing phototherapy chamber to mobile, easy portable units. This will enable to run the phototherapy in various stages of treatment, depending on the current needs of the patient. To verify the efficacy of these devices, several studies will be conducted involving both healthy volunteers and patients with neuropsychiatric disorders.

 

OPERATIONAL PROGRAMMES

OP Enterprise and Innovation for Competitivness

Research and Development of Phototherapy Mask for Seasonal Affective Disorder (CZ.01.1.02/0.0/0.0/17_107/0012517)
Investigator: PhDr. Jana Kopřivová, Ph.D.
Principle investigator: ELON Technologies s.r.o.
Co-investigator/Partner: NIMH
Duration: 1.1.2020–30.9.2021
Total budget: 18 860 156 CZK
Total budget NIMH: 4 564 886 CZK
The aim of the project is to develop a phototherapeutic mask to influence the circadian rhythms. The basic functional principle of the device is based on the technology of printed forms of electroluminescent light in the area of the blue light spectrum (460 - 480 nm). As part of the project we will develop an innovative, user-friendly hardware platform that will be able to detect phase shifts in circadian rhythms based on the user's physical activity. Subsequently, the light mask lighting mode will be individually tailored in order to influence circadian rhythms by retinal illumination during sleep. As a result, a non-invasive phototherapy device for home use by patients will be developed.

 

INTERNATIONAL PROJECTS

The Ministry of Education, Youth and Sports of The Czech Republic

Dynamics of Hippocampal and Neocortical Neuronal Representations of Mutual Relationships between a Subject, Significant Moving Objects, and Environment (LTAUSA19135)
Principle investigator: RNDr. Eduard Kelemen, Ph.D.
Investigator: Prof. Saak Victor Ovsepian, M.D., Ph.D.
Principle investigator: NIMH
Co-investigators/Partners: Institute of Physiology CAS; New York University (Prof. André A. Fenton), University of Arizona (Prof. Jean-Marc Fellous, Ph.D.)
Duration: 1.11.2019–31.12.2022
Total budget: 6 991 000 CZK
Total budget NIMH: 3 496 CZK
Abstract: Ability to orient and navigate in environment inhabited with moving objects, be it conspecifics, potential predators, prey or non-animate objects is crucial for survival and success in many animal species.  The main goal of the present project is to investigate in laboratory rat neural circuitry involved in controlling interaction with moving objects (conspecifics or a mobile robot) in an environment. The role of the hippocampus and neocortical areas in these cognitive processes has been already determined by our group. Now we plan to elucidate cellular and cell ensemble substrate of moving-goal navigation, which has so far remained relatively elusive. We aim to characterize patterns of activation of cortical networks in rats that are involved in processing interaction between the subject, moving objects and environments. We will use immediate early gene imaging and single cell ensemble electrophysiological approaches. To investigate causal relationship between neuronal activity patterns and rat’s interaction with moving objects we will use optogenetic manipulations of neocortical activity.

 

HORIZON 2020

Revolution of Sleep Diagnostics and Personalized Health Care Based on Digital Diagnostics and Therapeutics with Health Data Integration (SLEEP REVOLUTION) (H2020 965417)
Investigator: MUDr. Jitka Bušková, Ph.D.
Principle investigator: Haskolinn in Reykjavik EHF
Project partners: NUDZ + dalších 36 partnerů v konsorciu
Duration: 1.1.2021–31.12.2022
Total budget: 14 998 353,75 EUR
Total budget NIMH: 127 372,5 EUR
Abstract: Obstructive sleep apnea (OSA) is associated with various negative health consequences including increased risk of heart disease, hypertension and daytime sleepiness causing road accidents. The economic burden of OSA is rising as almost 1 billion people worldwide are estimated to have OSA. The current diagnostic metric, however, relates poorly to these symptoms and comorbidities. It merely measures the frequency of breathing cessations without assessing OSA severity in any other physiologically relevant way. Furthermore, the clinical methods for analyzing PSG signals are outdated, expensive and laborious. Due to this, the majority of OSA patients remain without diagnosis or have an inaccurate diagnosis leading to sub-optimal treatment. Thus, it is evident that more personalized diagnostics are required including predictive and preventive health care and patient participation. The SLEEP REVOLUTION aims to develop machine learning techniques to better estimate OSA severity and treatment needs to improve health outcomes and quality of life. These techniques are implemented to high-end wearables developed in this project to alleviate the costs and increase the availability of PSGs. Finally, we aim to design a digital platform that functions as a bridge between researchers, patients and healthcare professionals. We will achieve these ambitious goals throughout extensive collaboration between sleep specialists, computer scientists and industry partners. The collaboration network consists of over 30 sleep centers working together to provide the needed retrospective data (over 10.000 sleep studies). The multi-center prospective trials involve experts and end-users to assess and validate the new SLEEP REVOLUTION diagnostic algorithms, wearables and platforms. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies (over 8000 members), we have the unique possibility to create new standardized guidelines for sleep medicine in the EU. 

 

 


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