The role of Src kinase in the TrkB signaling pathway induced by sleep deprivation and sedative-anesthetic drugs

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dc.contributor Helsingin yliopisto, Bio- ja ympäristötieteellinen tiedekunta fi
dc.contributor University of Helsinki, Faculty of Biological and Environmental Sciences en
dc.contributor Helsingfors universitet, Bio- och miljövetenskapliga fakulteten sv
dc.contributor.author Michalowski, Piotr
dc.date.issued 2019
dc.identifier.uri URN:NBN:fi:hulib-201910303804
dc.identifier.uri http://hdl.handle.net/10138/306556
dc.description.abstract The TrkB signaling pathway plays an important role in synaptic transmission and plasticity. Synaptic plasticity is disrupted in many neurological disorders, such as major depression and dementia. A number of studies indicate that TrkB (tropomyosin-related kinase B) signaling is required for the therapeutic effects of antidepressants. Both conventional and rapid-acting antidepressants encompass the TrkB pathway but the underlying mechanism of this remains unknown. Recent studies have, however, revealed an intriguing link between emergence of slow wave EEG activity (SWA) or sedation and the TrkB pathway. Notably, various anesthetics and sedatives (e.g. isoflurane and medetomidine) that increase SWA concomitantly induce TrkB signalling, and this seems to happen independently of BDNF (brain-derived neurotrophic factor), the primary ligand of TrkB. Given the ability of Src kinase to transactivate TrkB in vitro, we have examined the acute effects of medetomidine and isoflurane on SrcY416 and TrkBY816 phosphorylation in the adult rodent cortex and hippocampus by using Western blotting. Pyrazolopyrimidine 2 (PP2), a Src kinase inhibitor, was implemented in order to inhibit TrkB signalling pathway induced by medetomidine. The study was further extended to sleep deprivation experiments to investigate the effects of deep sleep on the Src and TrkB protein phosphorylation. Phosphorylation of GSK3βS9, another important molecular event coupled with antidepressant effects, was also investigated. The results indicate that both isoflurane and medetomidine activate Src kinase and TrkB signalling pathway. Such an effect was not, however, seen in the PP2 study and thus we failed to confirm the mechanistic connection between Src and TrkB. A trend in the phosphorylation of TrkB, Src and GSK3β was found in the brain samples collected after 15 minutes of recovery sleep, suggesting that TrkB signalling is also facilitated during physiological SWA. In conclusion, these results reinforce the hypothesis that SWA occurs simultaneously with TrkB signaling. Future studies are required to test the involvement of Src kinase in this phenomenon. en
dc.language.iso eng
dc.publisher Helsingin yliopisto fi
dc.publisher University of Helsinki en
dc.publisher Helsingfors universitet sv
dc.subject Src kinase en
dc.subject TrkB signaling pathway en
dc.subject sleep deprivation en
dc.subject slow wave activity en
dc.title The role of Src kinase in the TrkB signaling pathway induced by sleep deprivation and sedative-anesthetic drugs en
dc.type.ontasot pro gradu -tutkielmat fi
dc.type.ontasot master's thesis en
dc.type.ontasot pro gradu-avhandlingar sv
dct.identifier.urn URN:NBN:fi:hulib-201910303804
dc.subject.specialization Solu- ja kehitysbiologia fi
dc.subject.specialization Cell and Developmental Biology en
dc.subject.specialization Cell- och utvecklingsbiologi sv
dc.subject.degreeprogram Genetiikan ja molekulaaristen biotieteiden maisteriohjelma fi
dc.subject.degreeprogram Master's Programme in Genetics and Molecular Biosciences en
dc.subject.degreeprogram Magisterprogrammet i genetik och molekylära biovetenskaper sv

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