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Modulation of central cholinergic neurotransmission
Valušková, Paulína ; Mysliveček, Jaromír (advisor) ; Cendelín, Jan (referee) ; Jakubík, Jan (referee)
Introduction: Central cholinergic system plays a key role in control of different brain functions such as learning, memory, attention, locomotion and rewards. Disrupted integrity, regulation or capacity of cholinergic signalling is closely connected with cognitive symptoms of several neurodegenerative and neuropsychiatric diseases, as Alzheimer disease, Parkinson disease, attention deficit hyperactivity disorder (ADHD), depression, schizophrenia and increased distractibility. The major neurotransmitter of cholinergic neurons is acetylcholine (ACh) and regulation of ACh levels is main pharmacotherapeutic approach to the treatment of diseases associated with central cholinergic system. The aim of the thesis was to study the changes of central cholinergic neurotransmission with respect to various aspects of modulation of ACh levels in the brain by controlling its release through M4 muscarinic receptors (MR), its hydrolysis by acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) and after hydrolysis in the synapse, regulation of the uptake of metabolite choline by high affinity choline transporter (CHT). Methods: Here we used telemetry to measure locomotor activity and body temperature in mice with selective deletion of M4 MR (M4KO) and their wild type (M4WT) controls under the basal conditions...
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Modulation of central cholinergic neurotransmission
Valušková, Paulína ; Mysliveček, Jaromír (advisor) ; Cendelín, Jan (referee) ; Jakubík, Jan (referee)
Introduction: Central cholinergic system plays a key role in control of different brain functions such as learning, memory, attention, locomotion and rewards. Disrupted integrity, regulation or capacity of cholinergic signalling is closely connected with cognitive symptoms of several neurodegenerative and neuropsychiatric diseases, as Alzheimer disease, Parkinson disease, attention deficit hyperactivity disorder (ADHD), depression, schizophrenia and increased distractibility. The major neurotransmitter of cholinergic neurons is acetylcholine (ACh) and regulation of ACh levels is main pharmacotherapeutic approach to the treatment of diseases associated with central cholinergic system. The aim of the thesis was to study the changes of central cholinergic neurotransmission with respect to various aspects of modulation of ACh levels in the brain by controlling its release through M4 muscarinic receptors (MR), its hydrolysis by acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) and after hydrolysis in the synapse, regulation of the uptake of metabolite choline by high affinity choline transporter (CHT). Methods: Here we used telemetry to measure locomotor activity and body temperature in mice with selective deletion of M4 MR (M4KO) and their wild type (M4WT) controls under the basal conditions...
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