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NMDA receptors outside CNS and their subunit composition
Hotovec, Matěj ; Kolcheva, Marharyta (advisor) ; Horáková, Olga (referee)
N-Methyl-D-Aspartate receptors (NMDARs) are a type of ionotropic glutamate receptor that is widely present in the central nervous system and in lesser numbers in other parts of the body, including the gastrointestinal tract. NMDARs play a crucial role in various physiological and pathological processes in the CNS, including synaptic plasticity, learning and memory, and excitotoxic damage. The role of NMDARs outside the CNS is still under investigation. This thesis aims to confirm the presence of NMDARs in the gastrointestinal tract and their subunit composition. Subunit specific NMDAR modulators showed effect on spontaneous phasic activity of ileum, indirectly confirming the presence of GluN1, GluN2A-D and GluN3 subunits. Attempt at direct evidence of protein expression by immunolabeling with monoclonal antibodies against NMDAR subunits was unsuccessful.
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Functional and pharmacological properties of GluN1/GluN2 and GluN1/GluN3 subtypes of NMDA receptors
Kolcheva, Marharyta ; Horák, Martin (advisor) ; Bohačiaková, Dáša (referee) ; Balaštík, Martin (referee)
(EN) N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors and they play a critical role in excitatory synaptic transmission in the mammalian central nervous system (CNS). Hyperactivity or hypoactivity of NMDARs can lead to a wide spectrum of pathological conditions and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, schizophrenia. NMDARs form a heterotetrameric complex made up of GluN1, GluN2(A-D) and/or GluN3(A, B) subunits. Different subtypes of NMDARs could have various effects on disease pathogenesis and therefore it is crucial to investigate the specific role of each subunit in the regulation of normal NMDAR functioning. The regulation of NMDARs occurs at different levels, from early processing, including synthesis, assembly, quality control in the endoplasmic reticulum (ER), trafficking to the cell surface, to internalization, recycling, and degradation. In this dissertation, we mainly focused on determining the roles of extracellular and transmembrane regions of different subtypes of NMDARs in the regulation of their function. In particular, using electrophysiology and microscopy methods on HEK293 cells and cultured hippocampal neurons, we investigated: (i) the impact of N-glycosylation and different lectins on...
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