Российская академия наук


EXPRESSION OF PRESENILIN 1 GENE EFFECTS DISTRIBUTION OF SYNAPTIC PROTEINS IN DROSOPHILA BRAIN



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EXPRESSION OF PRESENILIN 1 GENE EFFECTS DISTRIBUTION OF SYNAPTIC PROTEINS IN DROSOPHILA BRAIN

Bolshakova O.I., Zhuk A.A., Rodin D.I., Sarantseva S.V.

National Research Centre “Kurchatov Institute” B.P. Konstantinov Petersburg Nuclear Physics Institute, Gatchina, Russia; olya99991@yandex.ru
Mutations in amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) can lead to familial forms of Alzheimer disease (AD). Mutations of PS1 gene are responsible for approximately 50% of all cases of early-onset autosomal dominant form of AD. PS1 is an integral protein localized in neurons mostly in endoplasmic

reticulum. Mutations in PS1 are assumed to change the processing of APP which can lead to increased amount of the toxic 42-residue amyloid-β-peptide. PS1 can also participate in regulation of intracellular transport, cell adhesion and synaptic connections. Transgenic Drosophila melanogaster lines expressing human wild type PS1 and mutant PS1 as well as presynaptic marker synaptotagmin (syt1) and synaptobrevin (n-syb) linked to GFP were used to evaluate synaptic changes. Syt1 level correlates with formation of synaptic vesicles and density of mature neurons and drops dramatically in AD. Distribution of synaptobrevin reflects the entirety of cytoskeleton and may indicate synaptic dysfunction. Confocal microscopy was used for estimation of fluorescence intensity in 5, 15 and 25 days old flies. The level of GFP fluorescence intensity was measured in mushroom bodies that are responsible for memory and learning and in Kenyon cells. ImageJ was used for measuring of relative intensity. Flies expressing PS1 and amyloid-β-peptideshowed no significant change of syt1 and n-syb level in mushroom bodies throughout the experiment. At the same time we observed redistribution of synaptic proteins in different parts of mushroom body. Examination of Kenyon cells showed that in 25 days old flies there was a significant drop of syt1 level while level of n-syb didn’t change. Flies expressing mutated PS1 with P267S mutation and amyloid-β-peptide showed accumulation of syt1 and n-syb in Kenyon cells throughout the experiment as compared to mushroom bodies. Thus hyperexpression of human PS1leads to redistribution of presynaptic proteins in Drosophila brain.

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