Processes of intracellular and extracellular transport play one of the most important roles in the functioning of cells. Changes to transport mechanisms in a neuron can lead to the disruption of many cellular processes and even to cell death. It was shown that disruption of the processes of vesicular, axonal, and synaptic transport can lead to a number of diseases of the central nervous system, including Parkinson’s disease (PD). Here, we studied changes in the expression of genes whose protein products are involved in the transport processes (Snca, Drd2, Rab5a, Anxa2, and Nsf) in the brain tissues and peripheral blood of mice with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced models of PD. We detected changes in the expressions of Drd2, Anxa2, and Nsf at the earliest modeling stages. Additionally, we have identified conspicuous changes in the expression level of Anxa2 in the striatum and substantia nigra of mice with MPTP-induced models of PD in its early stages. These data clearly suggest the involvement of protein products in these genes in the earliest stages of the pathogenesis of PD.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Investigating individuals with the most identical genetic background is optimal for minimizing the genetic contribution to gene expression. These individuals include monozygotic twins discordant for PD. Monozygotic twins have the same genetic background, age, sex, and often similar environmental conditions. The aim of this study was to carry out a transcriptome analysis of the peripheral blood of three pairs of monozygotic twins discordant for PD. We identified the metabolic process “circadian behavior” as a priority process for further study. Different expression of genes included in the term “circadian behavior” confirms that this process is involved in PD pathogenesis. We found increased expression of three genes associated with circadian behavior, i.e., PTGDS, ADORA2A, and MTA1, in twins with PD. These genes can be considered as potential candidate genes for this disease.
1 September 2023 in Molecular Genetics, Microbiology and Virology
The Annexin 2 protein (ANXA2) encoded by the ANXA2 gene performs a number of biological functions that are primarily related to cellular transport. An impa
22 April 2024 in Molecular Genetics Microbiology and Virology (Russian version)
INTRODUCTION The Danio rerio (D. rerio) is one of the advanced targets for modelling pathological conditions. A large amount of such work in this case is carried out at the transcriptomic level. Transcriptomic studies require the use of stable housekeeping genes (HKG), so we selected candidate HKG and analyzed their stability in D. rerio under normal conditions. MATHERIAL AND METHODS The work was carried out using D. rerio (line AB) whose embryos were sampled at three time points: hatching stage (2 days post-fertilisation, dpf), early larvae stages (5 dpf and 9 dpf). The expression levels of HKGs were analyzed using real-time PCR. Further analysis of the obtained Ct results was performed in RefFinder software. RESULTS Different HKGs are suitable for assessing gene expression changes at different developmental stages of D.rerio. aars1 and polr2f is the optimal pair of HKGs at the hatching stage (2 dpf), aars1 and psmd6 are most suitable for the early larvae stage (5 dpf), bcat2 and actb1 are most suitable for 9 dpf. During the transcriptomic studies at several developmental stages simultaneously, it is necessary to use a single selected pair of HKGs for all investigated stages of development of D.rerio: aars1 and lsm12b. CONCLUSION According to the data obtained, aars1 and lsm12b are the most stable HKGs for all studied early developmental stages of D.rerio. In addition, we have shown for the first time that aars1 is the most stable HKG for the early stages of development. The second most stable HKG is lsm12b. Our data about the stability of the lsm12b gene are consistent with previously published data.
26 September 2023 in Molecular Genetics Microbiology and Virology (Russian version)
ВВЕДЕНИЕ Белок Annexin A2 (ANXA2), кодируемый геном ANXA2, выполняет целый ряд биологических функций, которые в первую очередь связаны с клеточным транспортом. Нарушения функциональной активности гена ANXA2 выявлены, в первую очередь, при опухолевых заболеваниях, однако, ранее нами было показано повышение экспрессии гена Anxa2 на уровне мРНК на ранних стадиях развития процессов нейродегенерации. В связи с этим наиболее интересным является изучение влияния подавления экспрессии гена ANXA2 на функционирование нервной системы на модели D. rerio с использованием морфолиновых олигонуклеотидов (морфолино). В работе исследовалось влияние морфолино к гену anxa2a на эмбриональное развитие Danio rerio. МАТЕРИАЛ И МЕТОДЫ Работу проводили с использованием рыб Danio rerio линии AB, эмбрионам которых делали инъекцию морфолиновых олигонуклеотидов к гену anxa2a. Оценка влияния вводимых морфолиновых олигонуклеотидов на эмбриональное развитие осуществляли посредством анализа изменения фенотипа на 2-й и 4-й дни после фертилизации (дпф). РЕЗУЛЬТАТЫ Введение экспериментальных морфолино, направленных на область старт-кодона и 5’НТО приводит к повышению процента деформаций по сравнению с группами Ко-Ин и Ко-Мо-D на 4-й дпф. Анализируемые деформации к 4-му дпф наблюдали как в контрольных, так и в экспериментальных группах. Помимо этого, нами была проанализирована более ранняя временная точка — на 2-й дпф. Изменения фенотипа на этой временной точке наблюдали только в экспериментальных группах. ЗАКЛЮЧЕНИЕ Сравнительный анализ данных, полученных при введении морфолино, направленных на старт-кодон и 5’НТО гена anxa2a, показал, что оба варианта могут быть использованы для дальнейших исследований. Также нами было показано, что наиболее предпочтительно проводить анализ экспрессии на 2-й дпф. Выявляемые на 2-й дпф эффекты, по всей видимости, являются специфичными, а наличие деформации заднемозгового желудочка позволяет предположить, что изменение экспрессии гена anxa2a может приводить к нарушению функционирования нервной системы.
1 June 2024 in Molecular Genetics, Microbiology and Virology
The zebrafish (Danio rerio) is one of the promising objects for modeling pathological conditions. A large number of such works are carried out at the trans