|
|
The effect of variations in GRIN genes on the biogenesis and functional properties of the NMDA receptor
Kuchtiak, Viktor ; Balík, Aleš (advisor) ; Rozbeský, Daniel (referee) ; Ladislav, Marek (referee)
The expression and activity of ionotropic glutamate receptors control signal transduction at the excitatory synapses in the central nervous system. The major class are the calcium-permeable NMDA receptors that are fundamental for the various forms of synaptic plasticity, a key mechanism in the process of learning and memory formation. NMDA receptors are heterotetrameric and are represented by three types of subunits: GluN1, GluN2A-D, and GluN3A-B. Each subunit consists of four domains, with the intracellular C-terminal domain accounting for up to half of the entire NMDA receptor subunit (GluN2A/2B). A body of evidence indicates that the hypofunction of the NMDA receptor plays an important role in the pathogenesis of several neuropsychiatric disorders, including schizophrenia. Schizophrenia is characterised by a high degree of heritability, but its genetic background is not yet fully understood. Previous studies have identified in the human genome several individual loci that contribute to disease susceptibility, including the GRIN genes encoding NMDA receptors. Using a sequencing approach, we identified and annotated genetic variations across all GRIN genes in a cohort of schizophrenia patients and control subjects. The submitted doctoral thesis focuses on the functional analysis of the genetic...
|
|
|
Role of glutamatergic transmission in mechanisms of addiction to morphine.
Moutelíková, Karolína ; Hejnová, Lucie (advisor) ; Červená, Kateřina (referee)
Drugs are used by mankind since ancient times. One group of these substances are opioids. Opioids have antinociceptive effects and can induce euphoria and relaxation as well. A chronic usage of opioids can lead to a development of drug addiction and phenomens like tolerance and sensitization. One of the most used opioids in medicine is morphine. Morphine is isolated from opium of poppy (Papaver somniferum). Direct effect of morphine is mediated via activation of μ- opioid receptors and their signal cascade. It was implicated that the usage of morphine affects other neurotransmmiter systems in the brain and these neurotransmmiter systems play a signifikant role in the development of addiction and other phenomena. One of these systems is an important excitatory brain system - glutamergic system. This bacherol thesis focuses on interrelationship between opioid and glutamatergic systems during addiction.There were described changes in a composition of glutame ionotropic receptors and changes in their expression as well as in expression of metabotropic glutamate receptors. These changes differ in various parts of the brain and in diverse stages of addiction on morphine too. In spite of all diferences, the results of studies indicate that glutamatergic receptors play a significant role in the development...
|
|
|
Role of glutamatergic transmission in mechanisms of addiction to morphine.
Moutelíková, Karolína ; Hejnová, Lucie (advisor) ; Červená, Kateřina (referee)
Drugs are used by mankind since ancient times. One group of these substances are opioids. Opioids have antinociceptive effects and can induce euphoria and relaxation as well. A chronic usage of opioids can lead to a development of drug addiction and phenomens like tolerance and sensitization. One of the most used opioids in medicine is morphine. Morphine is isolated from opium of poppy (Papaver somniferum). Direct effect of morphine is mediated via activation of μ- opioid receptors and their signal cascade. It was implicated that the usage of morphine affects other neurotransmmiter systems in the brain and these neurotransmmiter systems play a signifikant role in the development of addiction and other phenomena. One of these systems is an important excitatory brain system - glutamergic system. This bacherol thesis focuses on interrelationship between opioid and glutamatergic systems during addiction.There were described changes in a composition of glutame ionotropic receptors and changes in their expression as well as in expression of metabotropic glutamate receptors. These changes differ in various parts of the brain and in diverse stages of addiction on morphine too. In spite of all diferences, the results of studies indicate that glutamatergic receptors play a significant role in the development...
|
|
| |
|
| |
guest ::
