Title Utjecaj nedostatka receptora sličnog Tollu 2 na izražaj neuroplastina i ATPaza u mozgu miša Title (english) Influence of Toll-like receptor 2 deficiency on neuroplastin and ATPases expression in mouse brain Author Mario Stojanović Mentor Svjetlana Kalanj-Bognar (mentor)Committee member Dinko Mitrečić (predsjednik povjerenstva)Committee member Dubravka Švob Štrac (član povjerenstva)Committee member Jasminka Štefulj (član povjerenstva)Committee member Marija Heffer (član povjerenstva)Committee member Danka Grčević (član povjerenstva)Granter University of Zagreb Defense date and country 2023-03-24, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 61 - Medical sciences Abstract Dosadašnja istraživanja pokazala su da receptor sličan Toll-u 2 (TLR2) u mozgu sisavaca sudjeluje u neuroinflamaciji dok tijekom razvoja utječe na proliferacijski i diferencijacijski status progenitorskih stanica. Cilj ovog rada je bio utvrditi utjecaj nedostatka TLR2 na izražaj proteina uključenih u sinaptičku plastičnost (neuroplastin) i membranski prijenos iona (ATPaze tipa P) u mišjem mozgu. Provedena je analiza sinaptičkog proteoma, genske i proteinske ekspresije navedenih proteina, njihovog tkivnog i membranskog smještaja, utvrđen je gangliozidom i određena katalitička aktivnost ATPaza u uzorcima moždane kore, hipokampusa i malog mozga mišjeg modela s nedostatkom TLR2 u usporedbi s kontrolnim tkivom. Rezultati su pokazali da je nedostatak TLR2 u mišjem mozgu povezan s: a) značajnim promjenama sinaptičkog proteoma, posebice zastupljenosti proteina nužnih za regulaciju aksonskih projekcija i mijelinizacije, glutamatergičke transmisije i energetskog metabolizma; b) manjim izražajem neuroplastina u hipokampusu i malom mozgu što vjerojatno ukazuje na smanjenje broja sinapsi, dok utvrđena količina ATPaza tipa P upućuje na manji broj sinapsi hipokampusa i povećani broj astrocita u malom mozgu; c) većim izražajem i katalitičkom aktivnošću membranske kalcijeve ATPaze u hipokampusu, što govori u prilog poremećenog transporta kalcijevih iona; d) većim udjelom jednostavnog gangliozida GD3 u hipokampusu te većim udjelom složenih gangliozida GT1b i GQ1b u malom mozgu, što može odražavati promjenu membranske homeostaze i poremećene specifične membranske procese poput proliferacije i ionskog transporta. Zaključno, u ovom radu je dokazano da nedostatak TLR2 u mišjem mozgu utječe na izražaj i funkciju membranskih sustava neophodnih za sinaptičku plastičnost i ionski transport, što predstavlja temelj za daljnje istraživanje novih uloga TLR2 u moždanom tkivu sisavaca.
Abstract (english) Previous studies have shown that roles of Toll-like receptor 2 (TLR2) in mammalian brain encompass its involvement in neuroinflammation and neurodevelopmental processes such as proliferation and differentiation of neuronal progenitor cells. The aim of this study was to determine whether lack of TLR2 influences on the expression of proteins which participate in synaptic plasticity (neuroplastin) and membrane ion transport (P-type ATPases) in mouse brain. The variations of the synaptic proteome, gene and protein expression of neuroplastin and P-type ATPases as well as their tissue and membrane localization, ATPases catalytic activity, and gangliosidome were analyzed in the tissue samples of cortex, hippocampus, and cerebellum derived from mouse model lacking TLR2 in comparison to control tissue. Results demonstrate that the lack of TLR2 is associated with: a) adjustments in the synaptic proteome related markedly to protein systems involved in regulation of axon projections and myelinization, glutamatergic transmission, and energy metabolism; b) lower expression of neuroplastin in the hippocampus and cerebellum indicating potential loss of synapses, while detected variable content of P-type ATPases may suggest reduced number of synapses in the hippocampus and increased number of astrocytes in the cerebellum; c) higher expression and increased catalytic activity of plasma membrane calcium ATPase in hippocampus arguing for deranged calcium transport; d) increased ratio of simple ganglioside specie GD3 in the hippocampus and complex gangliosides GT1b and GQ1b in the cerebellum which may reflect alteration of membrane homeostasis and specific membrane functions such as proliferation and ion transport. In conclusion, presented findings reveal that the lack of TLR2 in mouse brain effects on the expression and function of membrane systems essential for synaptic plasticity and ion transport, opening new avenues for investigation of yet undescribed roles of TLR2 in the mammalian brain.
Keywords
Miševi
Proteom
Toll-u 2
ATPaze tip P
Neuroinflamatorne bolesti
Sinapse
Hipokampus
Cerebelum
Keywords (english)
Mice
Proteome
Toll-Like Receptor 2
P-type ATPases
Neuroinflammatory Diseases
Synapses
Hippocampus
Cerebellum
Language croatian URN:NBN urn:nbn:hr:105:832399 Project Number: IP-2016-06-8636 Project Number: DOK-2018-01-5001 Project Number: KK.01.1.1.01.0007 Study programme Title: Neuroscience Type of resource Text Extent 145 str. File origin Born digital Access conditions Embargoed access Terms of use Created on 2023-04-06 07:37:59
