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Cholinergic neurons and Alzheimer's disease
Machová, Eva ; Doležal, Vladimír (advisor) ; Krištofíková, Zdena (referee) ; Zvolský, Petr (referee)
Alzheimer's disease is a degenerative brain disorder. The incidence of the disease increases with age and every year the total number of affected persons is higher. The malfunction of various mental functions is a typical feature of Alzheimer's disease, including loss of short-term memory and development of personality changes. It is now generally accepted that the main cause of the disease is increased production of r3-amyloid fragments that mediate toxic effects and lead to r3-amyloid plaques formation. Alzheimer's disease and also normal aging are accompanied by a loss of cholinergic neurons and weakened cholinergic neurotransmission. In my thesis I dealt with changes in the brain chol inergic system during aging in control mice and in a mouse model of Alzheimer's disease (APPswe/PS1 dE9). In this context I also investigated in vitro influence of docosahexaenoic acid (w-3 essential fatty acid) changes in membrane cholesterol content on the expression of cholinergic phenotype in the NG108-1 5 cholinergic cell line. I also performed ex vivo experiments on rat brain cortex to investigate the characteristics of action of muscarin ic agonist xanomeline that was developed as a selective muscarinic agonist to strengthen signalization through the muscarinic M1 receptor in Alzheimer's disease. The experiments on...
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Psychosocial Aspects of Huntington's Disease
Uhrová, Tereza ; Roth, Jan (advisor) ; Zvolský, Petr (referee) ; Benetin, Ján (referee)
Huntington's disease (HD) is an autosomal dominant inherited neuro-psychiatric disease with usual onset in the middle age. The mutation, located on the short shoulder of chromosome 4, is an expansion of a nucleotide triplet, containing cytosine, adenine, guanine (CAG), with critical limit of 40+ repetitions. The principal symptoms include motor symptoms (chorea, dystonia, disorders of voluntary movements), progressive cognitive deterioration and neuropsychiatric symptoms (behaviour disorders, affective symptoms and so on). The clinical diagnosis is confirmed by a genetic test, which may also be carried out presymptomatically in offsprings of the diseased person. The objective of the 1st study consisted in the characterization of differences in psychiatric examination and neuropsychological testing among the people at risk (PAR), in whom it was recommended to delay the test, and people at risk, who were recommended to continue in the so-called predictive protocol. The total of 52 people have been examined (32 females, 20 males). In addition to the common psychiatric examination we have also administered the Eysenck Personality Questionnaire (EPQ-A), self-rating scale of general psychopathology (SCL- 90), three short cognitive tests - Trail making test, test of Verbal fluency and...
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Study of polymorphisms in candidate genes in the population of ADHD children
Kopečková, Marta ; Goetz, Petr (advisor) ; Šantavý, Jiří (referee) ; Kemlink, David (referee) ; Zvolský, Petr (referee)
The research of tbc way of participatioo of each Iransmitte ystem in pathology of ADHD cao be of belp. in tbe future, in tbe seleetion of the approprisle drug ss substances witb different mechanisms of functioniog are used to Ireat UlC byperklnctic syndrome. For our resear h the genes of dopominergic (DR02, DRD3 a DATl ). noradrenergic (OBH) and serotoninergic (5-HTT) systems were selected. ln these geoes I1 polymorphisms were analysed by molecular-genetic metbods based on sssociation slrategy "case-conlrol". Tbe presence of risk allcles was compared betweeo tbe sarople of 100 ADHD childreo BOd a coolrol group of 100 subjects, in whom tbc ADHD symptoms were excluded by Coooers' test. Tbc results of our research suggest tbc an association of thc gcnes witb ADI·ID. Specifically, after multiple testlng correction, sex correction, and power analysis, it could be coocJuded: I) tbe risk of ADHD is sigolficantJy lncreased in tbc presence oť one risk allele in genes DRD2 (7,5-fold), 5-HTT (2,7-fold) and DATl (l ,6-fold) 2) tbe risk of ADHD is significaotJy increased at homozygotes for risk alleles in genes DRD2 (54-fold), 5-HTT (6,7-fold) BOd DATl (6,6-fold) For polymorphisms G444A and Cl603T in DBH, which were detected by univariant analysis, baplotype artaIysis was performed and resultedln conclusion...
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Alzheimer's Disease and Family Caregiver Burden. Impact of Alzheimer's Disease on Family Caregiver Psychosocial Health.
Zvěřová, Martina ; Jirák, Roman (advisor) ; Holmerová, Iva (referee) ; Zvolský, Petr (referee)
Alzheimer's Disease is a progressive, irreversible neurodegenerative illness and the most common of the dementing disorders. Only few diseases disrupt patients and their relatives so completely or for so long a period of time as Alzheimer 's. Caring is held to be very demanding and emotionally involving. Caregiver burden has been defined as a multidimensional response to emotional, social, physical, psychological, and financial stressors associated with the caregiving experience. The objective of the 1st study was to assess the degree of burden and its possible change in family caregivers of the long-term sick family member with progressive Alzheimer's disease during eight-month monitoring. In addition to the common psychiatric examination the Mini- Mental State Examination (MMSE) was administered in patients to indicate the severity of the dementia and the Zarit Burden Interview was administered in caregivers to assessed degree of burden. The total of 60 people have been examined - 30 patients with AD and 30 their caregivers (24 females, 6 males) were recruited from the Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague. At the beginning of the study there were 18 patients with mild stage of AD (60%), 11 patients suffered...
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Psychosocial Aspects of Huntington's Disease
Uhrová, Tereza ; Roth, Jan (advisor) ; Zvolský, Petr (referee) ; Benetin, Ján (referee)
Huntington's disease (HD) is an autosomal dominant inherited neuro-psychiatric disease with usual onset in the middle age. The mutation, located on the short shoulder of chromosome 4, is an expansion of a nucleotide triplet, containing cytosine, adenine, guanine (CAG), with critical limit of 40+ repetitions. The principal symptoms include motor symptoms (chorea, dystonia, disorders of voluntary movements), progressive cognitive deterioration and neuropsychiatric symptoms (behaviour disorders, affective symptoms and so on). The clinical diagnosis is confirmed by a genetic test, which may also be carried out presymptomatically in offsprings of the diseased person. The objective of the 1st study consisted in the characterization of differences in psychiatric examination and neuropsychological testing among the people at risk (PAR), in whom it was recommended to delay the test, and people at risk, who were recommended to continue in the so-called predictive protocol. The total of 52 people have been examined (32 females, 20 males). In addition to the common psychiatric examination we have also administered the Eysenck Personality Questionnaire (EPQ-A), self-rating scale of general psychopathology (SCL- 90), three short cognitive tests - Trail making test, test of Verbal fluency and...
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Cholinergic neurons and Alzheimer's disease
Machová, Eva ; Doležal, Vladimír (advisor) ; Krištofíková, Zdena (referee) ; Zvolský, Petr (referee)
Alzheimer's disease is a degenerative brain disorder. The incidence of the disease increases with age and every year the total number of affected persons is higher. The malfunction of various mental functions is a typical feature of Alzheimer's disease, including loss of short-term memory and development of personality changes. It is now generally accepted that the main cause of the disease is increased production of r3-amyloid fragments that mediate toxic effects and lead to r3-amyloid plaques formation. Alzheimer's disease and also normal aging are accompanied by a loss of cholinergic neurons and weakened cholinergic neurotransmission. In my thesis I dealt with changes in the brain chol inergic system during aging in control mice and in a mouse model of Alzheimer's disease (APPswe/PS1 dE9). In this context I also investigated in vitro influence of docosahexaenoic acid (w-3 essential fatty acid) changes in membrane cholesterol content on the expression of cholinergic phenotype in the NG108-1 5 cholinergic cell line. I also performed ex vivo experiments on rat brain cortex to investigate the characteristics of action of muscarin ic agonist xanomeline that was developed as a selective muscarinic agonist to strengthen signalization through the muscarinic M1 receptor in Alzheimer's disease. The experiments on...
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