|
| |
|
|
Study of mechanisms influencing inflammatory and neurodegenerative processes and their subsequent treatment in ALS and spinal cord injury
Vargová, Ingrid ; Jendelová, Pavla (advisor) ; Jiruška, Přemysl (referee) ; Balaštík, Martin (referee)
Study of mechanisms influencing inflammatory and neurodegenerative processes and their subsequent treatment in models of ALS and spinal cord injury The mechanisms of neurodegeneration during spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) are complex and poorly understood, which is why it's troublesome to counteract them with effective therapies. This thesis explores the pathways of autophagy, endoplasmic reticulum (ER) stress, and the mammalian target of rapamycin (mTOR) pathway that regulates these mechanisms in models of both SCI and ALS. Upregulation of autophagy and the mTOR pathway in an in vivo contusion SCI injury model was confirmed. The mTOR inhibition led to upregulation of autophagy, reduction of inflammation, and recovery in acute SCI. Upregulated autophagy was discovered in the SOD1G93A rat model of ALS. By treating the ALS rats with human mesenchymal stem cells, prolonged survival of the animals and preservation of motor neurons (MNs) possibly occurred through modulation of autophagy. The involvement of the mTOR pathway in the degeneration of MNs was further explored in the context of astrocytes. Pleckstrin homology like domain family A member 3 (PHLDA3), a newly discovered repressor of the mTOR pathway, was found to lead to ER stress if overexpressed in astrocytes...
|
|
|
Adult neurogenesis in the hippocampus and spatial navigation
Dostálová, Magdalena ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
Hundreds to thousands of new granule neurons are born every day in the hippocampus within the whole life. Inspite of intensive research of the last decades, their function remains unclear. Their participation in spatial memory and the ability of orientation is assumed. Results from behavioral tests like the Morris water maze, the radial maze and many other testing tasks, are often contradictory. Nevertheless, it is highly probable that neurogenesis plays a role in pattern separation and long-term relational memory. Further studies and especially reliable methods of ablation and detection are required for deeper insight into this issue.
|
|
|
Neurogenesis in the adult brain, its regulation and possible functions
Pištíková, Adéla ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
In this thesis I examine neurogenesis in the adult brain. Neurogenesis takes place in two main neurogenic areas. One area is located at the side of the forebrain ventricle and the other in dentate gyrus of the hippocampus. The forebrain ventricle neurogenesis is important for olfactory discrimination and olfactory memory. In the hippocampus, its function is unclear, but there are several hypotheses about its possible significance. We assume it might function in pattern separation and also be involvedin preventing interference between memory traces. The last chapter I dedicate to the positive and negative regulation of neurogenesis. The manipulations enhancing neurogenesis include voluntary physical activity, enriched environment and SSRI antidepressants. The negative impact on neurogenesis is exerted among other factors by stress, irradiation and a cytostatic Temodal, which is used methodologiclly to block neurogenesis.
|
|
|
Otimization of a dose of temozolomide for efficient reduction of adult neurogenesis in the laboratory rat
Pištíková, Adéla ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
The goal of this study is to find an optimal dose of cytostatic Temozolomide (TMZ) for Long-Evans strain of rats. This dose should reduce neurogeneis while having a minimal pernicious health side-effects. Temozolomide is newly used to suppress neurogenesis but similarly to any other cytostatic has an effect on all dividing cells in an organism. This can affect health of an animal. Contrary to the mice, there was no systematic attempt to establish optimal dose. In our experiment rats were divided into four groups - one control group and three treatment groups which received different doses of temozolomide (10, 25, 40 mg/kg of TMZ). To detect level of neurogenesis cells were labeled by bromodeoxyuridine. During the experiment blood element counts were assessed, sensorimotoric tests were conducted, and weight increment was monitored. The results indicate that dose of 10mg/kg is adequate as it reduces neurogenesis by 64% compared to the control group and does not significantly differ from higher doses. In this group weight increment is comparable with the control group, while in the higher doses of TMZ weight increment is significantly lower. Effect of myelosupression is same for all treatment groups.
|
|
|
The pathogenesis of autism in relation to maternal antibodies: from molecule to connectome
Rusková, Lívia ; Jiruška, Přemysl (advisor) ; Míková, Hana (referee)
Autism is a neurological disease that affects predominantly boys. It is characterised by anti- social and stereotypical behaviour with a low level of empathy. Most of the studies have been focusing on the genetic aetiology of this disease, however in the past years research has focused on the role of maternal immune system. This thesis is putting together information predominantly about maternal autoimmune antibodies that recognize specific proteins important in neurogenesis. It is focusing on the function of these proteins in neurogenesis and their possible correlation with the pathological brain connectome in autism. Key words: autism, maternal antibodies, connectome, neurodevelopment
|
|
|
Acute effects of central muscarinic antagonist scopolamine on learning in two cognitive tasks: Comparison of Long-Evans and Wistar outbred rat strains
Entlerová, Marie ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee)
Spatial navigation is essential for survival not only in mammals. Neural and neuropharmacological changes of learning and memory in humans and rats could be measured through their behavior and responses to stimuli. In focus of experimental models of cognitive deficits, the Morris water maze (MWM) represents a clasiccal test of exact allothetic representation, i.e. the cognitive map. Another important test of spatial navigation is the active place avoidance, or Carousel maze (also AAPA, Active Allothetic Place Avoidance), that can be used to test the ability of cognitive coordination, thus the ability to distinguish relevant stimuli from irrelevant. There are analogous tasks for testing cognitive abilities in humans for both tests (e.g. Blue Velvet Arena for MWM, virtual reality simulations on PC for AAPA, etc.). Aim of the present study is to compare the sensitivity of outbred Long-Evans and Wistar strains of rats from the institutional breeding to the acute administration of scopolamine, the antagonist of central muscarinic acetylcholine receptors, at doses 0.8 mg/kg; 1.5 mg/kg and 3.0 mg/kg. The results show that the Wistar strain is more influenced by cholinergic blockade than Long-Evans strain in both AAPA and the MWM. Furthermore, it appears that the control rat strain Long-Evans have better...
|
|
|
Functional consequences of epileptic seizures and CNS hypoxia-ischemia
Krýsl, David ; Mareš, Jan (advisor) ; Druga, Rastislav (referee) ; Jiruška, Přemysl (referee)
Hypoxic - ischemic CNS lesions and epileptic seizures share many common pathophysiologic features. Basic mechanisms , either detrimental ( excitotoxicity , free radicals, inflammation , changes in permeability of the blood brain barrier , particularly necrotic and apoptotic cell death) , or reparative ( gliosis , neuroplasticity , neurogenesis , vascular proliferation ) occur in Both types of damage , but may be expressed in varying degrees, and may take place in different time term. Hypoxia , but also global and focal ischemia, CNS are in humans and in experimental models under certain conditions accompanied by epileptic seizures. Epileptic seizures vice versa acutely and chronically affect cerebral blood flow (CBF ) . CBF and cerebral metabolism is significantly affected during status epilepticus ( SE). CBF changes can significantly contribute to pathophysiological consequences of seizures and may have links with some of their clinical manifestations (eg Todd's postparoxysmální hemiparesis ( MS Mathews et al. , 2008; Yarnell PR 1975) ) . Focal ischemia, CNS has often consequences in distant , but functionally linked areas ( diaschisis ) . There is a remote influence not only the blood flow and metabolism , but also excitability (Andrews, RJ , 1991 Buchkremer - Ratzmann I. et al. 1996b ) . Also in the...
|
|
|
Spatial memory in humans and its disorders: From animal models towards schizophrenia
Fajnerová, Iveta ; Vlček, Kamil (advisor) ; Rokyta, Richard (referee) ; Jiruška, Přemysl (referee)
Spatial memory is often studied using spatial tasks originally developed for animals, such as the Morris water maze and the Carousel maze tasks. Both tasks have an important role in the process of identification of brain areas crucial for spatial memory, and also in pharmacological research of animal models of neuropsychiatric diseases. In recent years considerable attention has been devoted to the research and treatment of cognitive impairment in schizophrenia. Comparative research addressing cognitive abilities of both animals and patients in similar tasks, could therefore lead to verification of the predictive and face validity of animal models of this complex disorder. The aim of this study was to create virtual analogues of these tasks, which would allow this comparative approach. This thesis first describes the experiment testing the performance of an animal model of schizophrenia induced by the application of dizocilpine (MK-801) in reversal version of both mentioned spatial tasks, in order to assess mental flexibility and learning abilities affected in schizophrenia. Other two experiments present the findings of the two virtual analogues tested in the first episode of schizophrenia patients. Our results confirm the presence of deficits in spatial memory and mental flexibility, functions dependent on...
|
|
|
Hippocampal neuronal representation of a moving object in a novel spatial avoidance task
Ahuja, Nikhil ; Stuchlík, Aleš (advisor) ; Jiruška, Přemysl (referee) ; Telenský, Petr (referee)
In real world environments, animals need to organize their behavior relative to other moving animals or objects; when hunting a predator, when migrating in groups or during various social interactions. In all of these situations, the animal needs to orient relative to another moving animal/object. To understand the role of the hippocampus in this ability we adopted a two-step approach. We developed a task that would mimic important elements of this behavior in the laboratory. The task required the rats to assess not only their distance from the moving object but also their position relative to the object. We further studied how neurons in the hippocampal CA1 subfield encode the subject, the moving object and the environment in the behavioral paradigm and how do these representations interact among themselves. In rats, we aimed to characterize spatial behaviors relative to moving objects and to explore the cognitive mechanisms controlling these behaviors. Three groups of animals were trained to avoid a mild foot-shock delivered in one of three positions: either in front, on the left side, or the right side of a moving robot. Using different variations of the task, we also probed whether avoidance was simply due to increased noise level or size of the retinal image or appearance of the robot. As the...
|
guest ::
RSS feed.