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The role of striatal cholinergic signalling in the control of behaviour
Abbondanza, Alice ; Jakubík, Jan (advisor) ; Bellone, Camilla (referee) ; Svoboda, Jan (referee)
Cholinergic transmission regulates many behavioural domains, ranging from motor activity to cognition. Acetylcholine signalling is mediated by muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively). While mAChRs are slow responding metabotropic receptors, nAChRs are ion channels, mediating fast neurotransmission. There is a growing body of evidence suggesting a role of nAChRs as important modulators of behavioural functions. However, as nAChRs consist of many subtypes, depending on their composition in subunits, and as they are expressed by various neuronal populations in different brain regions, their contribution to behavioural control is very complex. To decipher their contribution, it is necessary to selectively target nAChRs expressed not only in particular regions but also by particular neurons with a defined effect on local microcircuits. The goal of the present thesis was to use different genetic strategies to induce regional- and cell-specific deletion of β2-containing nAChRs in the mouse brain, in order to characterize the functional role of these receptors. We focused our work in two brain areas, the striatum and the prefrontal cortex (PFC). In the striatum, we identified the striatal neurons that express one of the most common nicotinic subunits, the β2...
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Targeting cholinergic system in tretment of Alzheimer's disease.
Golianová, Nikoleta ; Jakubík, Jan (advisor) ; Říčný, Jan (referee)
Alzheimer's disease (AD) is a neurodegenerative disorder of CNS and very serious type of dementia. AD affected 46.8 million people worldwide in 2015, and it is estimated that the number of patients will double every 20 years, reaching over 130 million people in 2050 according to Alzheimer's Disease International. There are two forms of the AD: familial (FAD) and sporadic (SAD) form. FAD is an early-onset disease caused by genetic mutations. SAD is more common, a late-onset disease with the age and ε allele of apolipoprotein E as major risk factors. The most crucial symptom is memory disorder, followed by disorientation, confusion, depression and later on, serious psychical and motor-skill problems. These symptoms are the result of a neuronal loss due to formation of β-amyloid oligomers and neurofibrillary tangles in the central nervous system (CNS). As for now, there are neither efficient diagnostic approaches, nor therapeutic ways to stop the degeneration of the brain. There are some drugs available, such as inhibitors of acetylcholinesterase, that have proven to slow down the progression of the AD. Other cholinergic approaches have been developed, but they have shown a lot of side effects, as they are targeting a large scale of receptors. Additional approaches are focusing on clearance of -...
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