Utjecaj kroničnoga stresa i starenja na lipidne splavi moždanih stanica u štakora [Influence of chronic stress and aging on lipid rafts in rat brain cells]

Balog, Marta (2019) Utjecaj kroničnoga stresa i starenja na lipidne splavi moždanih stanica u štakora [Influence of chronic stress and aging on lipid rafts in rat brain cells]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

The main hypothesis of this thesis proposed that aging and stress combined lead towards changes in lipid rafts composition of brain and trigger neurodegeneration mediated by location shift of lipid raft proteins in hippocampus – insulin and leptin receptor. In experiments performed in this thesis diminished memory in older females was observed and was followed by reduced expression of insulin and AMPA receptors in hippocampus of older animals. Leptin receptor was activated upon stress in older animals and could be a potential neuroprotection activator. Also, it was determined that both – insulin and leptin receptors are not located inside lipid rafts of hippocampus and cerebellum as considered up to now by peripheral tissue analysis. Lipid content changes of lipid rafts upon stress were noticed as GM1 ganglioside expression increase in CA1 and dentate gyrus of hippocampus of young animals and increase of GD1a expression in CA1 region of hippocampus in all chronically stressed animal groups. Also, colocalization of amyloid precursor protein and GD1a was observed in hippocampus of older females as a result of chronic stress response. If insulin and leptin receptors expression is decreased, AMPA receptor and neuroplastin follow this trend. It implies a connection of leptin and insulin signalling pathways with pathways involved with neuroplasticity. During experimental part of this thesis, a unique animal model of sex and age specific chronic stress was developed that implies strong chronic stress resistance of young animals. It was observed that chronic stress had the strongest impact in older females and that stress regulation in the brain is sex and age specific.

Abstract in Croatian

Glavna je hipoteza ove disertacije pretpostavila kako starenje i stress dovode do promjena sastava lipidnih splavi stanica mozga te okidaju neurodegenerativne promjene posredovane promjenom smještaja i izražaja proteina u hipokampusu i malom mozgu koji se nalaze unutar lipidnih splavi – inzulinskog i leptinskog receptora. Pri izradi disertacije uočen je utjecaj stresa na smanjeno pamćenje u slučaju starijih ženki koje također prati i smanjeni izražaj inzulinskog i AMPA receptora u hipokampusu starijih životinja. Leptinski receptor pokazuje snažnu aktivaciju u starijih životinja u uvjetima stresa i može se smatrati zaštitnim mehanizmom od neurodegeneracije tijekom izloženosti kroničnom stresu. Osim toga, zanimljiv je nalaz kako se inzulinski i leptinski receptori ne nalaze unutar lipidnih splavi hipokampusa i malog mozga kako je do sada smatrano analizom perifernih tkiva. Promjene lipidnog sastava lipidnih splavi u uvjetima stresa uočene su u obliku povećanja GM1 gangliozida u CA1 i dentatnom girusu hipokampusa u mladim životinjama, te povećanju GD1a gangliozida u CA1 području svih skupina životinja u uvjetima stresa. Također je uočena snažna kolokalizacija preteče amiloida i GD1a u hipokampusu starijih ženki kao posljedica kroničnog stresa. U slučaju sniženog izražaja inzulinskog i leptinskog receptora, snižavaju se i izražaji neuroplastina i AMPA receptora u starijih mužjaka što povezuje signalne puteve inzulina i leptina s putevima važnim za krajni ishod neuroplastičnosti. Tijekom izrade ove disertacije razvijen je jedinstveni spolno i dobno specifičan animalni model kroničnog stresa koji upućuje na snažnu otpornost mladih životinja na kronični stres, a najviše su na stres osjetljive starije ženke. Također je uočena spolno i dobno specifična regulacija stresa u mozgu.

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