|
|
Hippocampus Dysfunction in Quinpirole Sensitization Model of Obsessive-Compulsive Disorder
Brožka, Hana ; Stuchlík, Aleš (advisor) ; Jendelová, Pavla (referee) ; Kelemen, Eduard (referee)
Obsessive-compulsive disorder (OCD) is a serious psychiatric condition manifested by repeated thoughts followed by stereotypic compulsive behavior. Alterations to cortico-thalamo-striato- cortical circuits are most often implicated in the pathophysiology of OCD. However, many studies have also found a changed volume, shape and activity of the hippocampus in OCD patients. This work focused on the activity of hippocampal CA1 cells during stereotypical checking behavior and on cognitive flexibility in a quinpirole (QNP) sensitization model of OCD. The activity of CA1 hippocampal cells during stereotypical checking was assessed in an enriched open-field test in QNP sensitized rats. Arc+ (activity-regulated cytoskeletal associated protein, or Arg 3.1) mRNA expression profiles were determined in CA1 coronal hippocampal sections following stereotypical checking. After the establishment of stereotypical checking (10 sessions), rats were exposed to the arena and sacrificed after 5 minutes. QNP sensitized animals visited the same objects with the same frequency as during previous sessions, while control rats did not. Locomotor activity was comparable between QNP treated rats and controls. Following sacrifice, rat brains were flash frozen and sliced to 20 µm thick sections. Sections, mounted on slides, were hybridized...
|
|
|
The establishment of invariable behaviour of rats in novel one-trial trace association task (OTTAT)
Alexová, Daniela ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Animal episodic-like memory tasks represent important component of episodic memory research. However, currently available episodic-like memory tasks are not based on episodic-like memory or encompass important caveats. In our laboratory, we recently devised a novel one-trial trace association task (OTTAT) to examine one-time associations of temporally discontinuous stimuli. This thesis deals with the improvement of OTTAT protocol by rat strain and compartment divider ('doors') selection which optimally promote the establishment of invariable behaviour of rats in OTTAT. Moreover, the accuracy of one-trial associations is also assessed by determining specificity of "rapid escape" response to conditioned stimulus of given sound characteristics. In Experiment 1, rats (Sprague-Dawley (SD), n = 36; Wistar (WI), n = 17; Long-Evans (LE), n = 8) were habituated 15 min daily for 3 days with standard doors (9 x 11 cm opening) to modified light and dark apparatus. The number of transfers between compartments and values of time spent in dark compartment obtained from 3rd habituation session were evaluated as indicators of invariable behaviour of rats. We found WI rats spend significantly more time in dark compartment than LE (p = 0.002) and SD rats (p = 0.001) and have significantly fewer transfers than LE rats...
|
|
|
The role of m6A pathway in regulation of cognitive function in a rat model of Alzheimer's disease and caloric restriction
Pohanová, Petra ; Telenský, Petr (advisor) ; Stuchlík, Aleš (referee)
Reversible adenosine methylation (N6-methylation; m6A) at the RNA level was described in connection to the regulation of RNA fate. The N6-methyladenosine pathway is important for cognitive function and mechanisms related to memory, including the regulation of adult neurogenesis and synaptic plasticity. The objective of this study was to test the hypothesis that a decreased activity of the RNA-demethylase FTO is associated with improved cognitive function in rats. The RNA-demethylase FTO is a key regulator of the m6A pathway. In this study, we administered MO-I-500, a pharmacological inhibitor of FTO in TgF344-AD transgenic rats, which resulted in an improvement of spatial cognition. We further investigated the cognitive enhancement induced by a caloric restriction as a possible compensatory mechanism of cognitive disorders and its effect on the proteins regulating the N6-methyladenosine pathway. Long-term caloric restriction ameliorated cognitive functions and led to changes in the expression of the major proteins controlling the m6A pathway (FTO, METTL3) which are consistent with the aforementioned hypothesis. Although we do not know the exact mechanism of action, these findings support the hypothesis that m6A pathway regulators, such as the FTO demethylase, may be a promising molecular target for...
|
|
|
Inflammation as a mechanism of neuropsychiatric disorders and role of physical activity.
Hlaváček, Vojtěch ; Stuchlík, Aleš (advisor) ; Vrajová, Monika (referee)
Psychiatric disorders are becoming an increasing problem and possess a socio-economic burden on societies worldwide. There has been an association between inflammation and psychiatric disorders for some time now, but the causal relationships and mechanisms are not fully understood yet. Better understanding of those mechanisms could help us in dividing patients into different mechanistic subtypes which could react differently to a treatment. That way we could prescribe the most effective treatment depending on the mechanism involved. Inflammation is sensitizing an individual to react in more pro-inflammatory fashion to a stressor leading to chronically inflamed states. This is something that we can observe in an array of mechanisms, which creates many positive inflammatory feedback loops. Those feedback loops are very hard to interrupt, because they reinforce each other, plus the immune system is overreacting to subsequent stressor creating a vicious cycle. This could potentially lead to development of neurodegenerative diseases. As it turns out, physical activity acts on several of those mechanisms involved in inflammatory feedback loops at the same time, making it an ideal prevention/treatment candidate. It plays a huge role in regulation of inflammation in anti-inflammatory manner and might be...
|
|
| |
|
|
Spatial Navigation Impairment as An EarlyMarker of Neurodegenerative Disease
Mokrišová, Ivana ; Hort, Jakub (advisor) ; Stuchlík, Aleš (referee) ; Vymazal, Josef (referee)
Aging of population with related increase of incidence of neurodegenerative diseases mostly Alzheimer disease (AD), poses a serious socioeconomic problem. In the recent years, research has been focused on specific early disease markers and identifications of patient's populations at increased risk of AD, which comprise mild cognitive impairment (MCI) and subjective cognitive decline (SCD) which may represent prodromal and preclinical stage of AD, while still preserving functional capacity. This thesis summarizes and further extends current knowledge in the field of AD with a specific focus on early disease markers. The main topic of the thesis is spatial navigation, especially its allocentric component and path integration. Examination of spatial navigation might serve as the valuable diagnostic tool which could be used in wider clinical practice for timely diagnostics, disease monitoring and also for evaluation of the treatment effect. We also present here experimental tests (questionnaires of subjective spatial navigation complaints and tests of visual perception) that have enough sensitivity and specificity for identification of subjects at risk for AD.
|
|
|
Coding of stable and moving objects in the brain
Lobellová, Veronika ; Stuchlík, Aleš (advisor) ; Telenský, Petr (referee)
Spatial navigation in an environment is essential for one's survival. Animals need to monitor location of self and location of other animate or inanimate objects. Navigation is a hippocampus dependent process supported by activity of place cells. Object location in space is thought to be coded as a point of interest on cognitive map formed by place cells. Place cells change their firing fields, process known as remapping, when a new object is introduced into the environment. However we do not yet know how location of moving objects such as predators or other animals is presented on the cognitive map. This work summarizes findings of chosen studies concerning the role of hippocampus and place cells in spatial coding of stable and moving objects.
|
|
|
Role of glutamate in obsessive-compulsive disorder: clinical and experimental findings
Mainerová, Karolína ; Stuchlík, Aleš (advisor) ; Fajnerová, Iveta (referee)
Obsessive - compulsive disorder is a common and chronic illness that decreases quality of life and leads to serious limitations. Its treatment is currently only successful in some patients and many of them remain with their problems without proper help and medication. The exact cause of the disease is not yet known, but the role of the glutamatergic system in the pathophysiology of obsessive-compulsive disorder is apparently very important and its modulation can potentially lead to increase in treatment success. Animal models of genetic, behavioural, pharmacological and optogenetic origins are very useful in gaining new insights into the principles and underlying causes of the disease. Clinical studies indicate the efficacy of glutamatergic modulators for disease manifestations and could serve as new avenues for the development of new drugs. Key words: obsessive-compulsive disorder (OCD); glutamate, animal model, clinical findings
|
|
|
Role of interneurons and neural circuit dysfunctions in Alzheimer's disease
Rakovets, Yuliia ; Stuchlík, Aleš (advisor) ; Červená, Kateřina (referee)
Alzheimer's disease is one of the most common neurodegenerative disorder that results in altered network activity, in particular cognitive decline. Majority people with AD experience memory impairment, poor judgment, disorientation and learning difficulties. Several hypotheses try to explain the cause of the disease, but it's poorly understood. Due to the fact that changes in brain structure arise years before clinical symptoms emerge, the available therapeutic treatments can only reduce the impact of neurodegeneration, but not to reverse. Interneurons, as a part of neural circuits, play an important role in the formation of cognitive abilities. Most of interneurons in CNS are inhibitory and they effectively control the network synchrony. Network hypersynchrony is an increased synchronization of neural activity and it's linked to AD pathology. Dysfunction of interneurons is resulted in altered network activity in patients with AD. Keywords: AD, brain, rat, interneurons, hypersynchrony.
|
|
|
Dysfunctions of interneurons in schizophrenia
Hrůzová, Karolína ; Stuchlík, Aleš (advisor) ; Weissová, Kamila (referee)
Schizophrenia is a serious neuropsychiatric disorder characterised by abnormal behaviours, perception and thoughts. It is a neurodevelopmental disease of two types of factors - genetic predispositions and environmental factors. The exact cause of schizophrenia remains, however, elusive. Interneurons are types of neurons, mostly exerting inhibitory action and their dysfunctions are associated with pathogenesis of schizophrenia. They are essential in the generation of neuronal oscillations, which play an important role in cognitive functions. Disruption of these oscillations (especially gamma band) could be paralleled by negative, positive or cognitive symptoms of schizophrenia. These interactions could be possible discerned with an innovative technique called optogenetics. Optogenetics is a combination of genetic and optical approaches to controlling activity of specific targeted neurons. With this method we can study animal models of schizophrenia with great insight, which could give us an explanation of abnormalities in behaviour caused by neuronal disruption. Keywords: schizophrenia; interneurons; animal models; neuronal oscillations; optogenetics
|
guest ::
