MAPK pathways and alphaB-crystallin phosphorylation in brain: a focus on aging and Alzheimer’s disease

Poster (download) Natalia Muraleva11Institute of Cytology and Genetics SB RAS Novosibirsk, Russia, myraleva@bionet.nsc.ru Accumulation of intracellular damage and protein aggregates is an universal hallmark of aging and accompanies the development of some age-related diseases include Alzheimer’s disease (AD). Alpha-B-Crystallin (CryaB) as the molecular chaperone contributes maintenance of proteostasis by prevention of aggregation of proteins (e.g. amyloid beta) and enables their correct refolding. CryaB activity is regulated by MAPK signaling pathway (MAPKsp) through its phosphorylation. Nevertheless, the link between changes in MAPK-dependent CryaB phosphorylation with age and the development of AD remains unclear. Here, we examined p38 MAPK- and ERK-dependent phosphorylation of CryaB in the brain of Wistar rats with normal aging and senescence-accelerated OXYS rats at the different stages of the development of AD-like pathology, including the presymptomatic stage.  The most significant changes identified in the p38 MAPK-dependent CryaB phosphorylation. The level of p-Ser59-CryaB in the brain of Wistar rats increased with the age on the background of p38-MAPKsp activation. Similar but more significant changes accompanied the development of AD-like pathology in OXYS rats. The activation of ERK1/2-dependent CryaB phosphorylation (p-Ser45-CryaB) was detected at the early age and at the late stages of AD-like pathology in OXYS, while changes in the ERK1/2 signaling pathway were detected in Wistar rats with age. Thus, alteration of MAPK-dependent phosphorylation CryaB occurs with the normal aging. Manifestation and progression of the signs of the AD occurs against the background of activation of p38MAPK-dependent phosphorylation of CryaB. Activation of EPK-dependent CryaB phosphorylation is characteristic of the preclinical and progressive stage of the AD-like pathology.

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Effects of melatonin and SkQ1 long-term treatment during aging and development AMD-like retinopathy

Poster (download) Darya V. Telegina1, Oyuna S. Kozhevnikova2, Anzhela Z. Fursova31ICG SB RAS, Novosibirsk, Russia, telegina@bionet.nsc.ru2ICG SB RAS, Novosibirsk, Russia, oidopova@bionet.nsc.ru3ICG SB RAS, Novosibirsk, Russia, anzhellafursova@yandex.ru Melatonin and antioxidant SkQ1 act like mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels and they may prevent mitochondrial damage during retinal aging and development of age-related retinal disease such as age-related macular degeneration (AMD). However, detailed effects of melatonin and SkQ1 on the biochemical mechanisms underlying therapeutic effect of these drugs during retinal aging and AMD progression remain unclear.В  Using Wistar rats with normal aging process and senescence-accelerated OXYS rats, which spontaneously develop a phenotype similar to human age-related disorders including AMD-like retinopathy, we found that treatment of SkQ1 and melatonin decreased the incidence and severity of retinopathy in OXYS rats. In Wistar rats, which do not naturally develop retinopathy, ophthalmoscopic inspections did not reveal pathological alterations in the retina of melatonin and SkQ1-treated rats. SkQ1 decreased p62/SQSTM1 protein but not mRNA levels in both OXYS and Wistar rat\’s retinas as compared of control rats. We observed reduced level of VDAC1 and increased level of glutaminase by long-term treatment of melatonin and SkQ1 in retina of Wistar rats but not OXYS rats. Taken together, our data indicated that long-term treatment of melatonin and mitochondria-targeted antioxidant SkQ1 may retard an age-related decline in the adaptability of retinal cells and may be considered as a strategy to slow down AMD. At the same time effects of melatonin and SkQ1 on molecular events may be different depending on genotype and disease.

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Methylation and expression profiles in Apoe vicinity point to specific neighboring interaction of Apoe and TOMM40 genes: implication for The Alzheimer disease.

Vladimir Babenko11Institute of Cytology and Genetics SB_RAS, bob@bionet.nsc.ru We assessed the dynamics of 8 genes including TOMM40, Apoe and other adjacent ones for overall chromatin marks landscape, including methylation profiles across ENCODE brain cell lines, and histone and ctcf marks. We revealed the region manifests Hi-C topology dynamics in a cell-specific manner. Additionally, based on methylation and histone marks profiles we underscore competitive manner of genes expression implying disrupted locus wide genes expression balance in Alzheimer patients due to Apoe extended locus methylation profile alteration.

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Search for single nucleotide polymorphisms (SNPs) associated with hypertension in the genome of senescence-accelerated OXYS rats

Poster (download) Vasiliy A. Devyatkin1, Natalia A. Muraleva2, Olga E. Redina3, Nataliya Kolosova41Institute of Cytology and Genetics SB RAS, devyatkin@bionet.nsc.ru2Institute of Cytology and Genetics SB RAS, myraleva@bionet.nsc.ru3Institute of Cytology and Genetics SB RAS, oredina@bionet.nsc.ru4Institute of Cytology and Genetics SB RAS, Nnnnn80@ngs.ru Aging is a risk factor for many diseases, but the likelihood of developing with age also depends on genetic factors, environmental conditions, lifestyle, and the presence of other pathologies. The OXYS rat strain (ICG SB RAS) is a unique model for studying the mechanisms of aging, as already at an early age these animals develop a whole complex of age-dependent diseases, including cataracts, retinopathy, osteoporosis, hypertension and Alzheimer’s-like pathology. Although hypertension has risk factors typical of age-related diseases, it itself is a risk factor for many other pathologies. However, the complex senile phenotype does not appear in other hypertensive models, even with higher blood pressure. The aim of this study was, based on the results of RNA-Seq, the search for single nucleotide polymorphisms that could contribute to the development of hypertension in OXYS rats with accelerated aging. We found that OXYS rats are genetically far from other strains and presumably have their own bases for the development of hypertension, which may determine the absence of the senile phenotype of OXYS rats in hypertensive rat strains.

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Age-related difference in use-dependent plasticity after divergent thinking session matches posterior-anterior shift in aging (PASA) model.

Poster (download) Evgeniya Privodnova1, Nina Volf2, Ekaterina Merculova3, Dariya Bazovkina41Scientific Research Institute of Physiology and Basic Medicine, privodnovaeu@physiol.ru2Scientific Research Institute of Physiology and Basic Medicine, volf@physiol.ru3Scientific Research Institute of Physiology and Basic Medicine, merkaterine@gmail.com4Scientific Research Institute of Physiology and Basic Medicine, daryabazovkina@gmail.com Repetitive cognitive activity has the potential to improve cognitive functioning through neuroplasticity. Despite evidence for task-specific traces after task performance in young adults, age differences of experience-related neuroplasticity remains understudied. Common patterns of age-related changes in brain activity across a variety of cognitive functions suggest the hemispheric asymmetry reduction in older adults (HAROLD) and the posterior-to-anterior shift in aging (PASA). We can expect that those models appear as age specificity of experience-related neuroplasticity. The aim of the current study was to investigate the age-related specificity in use-dependent changes between pre-training and post-training baseline alpha EEG rhythm measures. 31 younger (Mean age = 21.3) and 30 older adults (Mean age=64.2) underwent a divergent thinking training session with concomitant 52-channel EEG registration. Upper alpha power was calculated via Fourier transform; current source density estimates and statistical nonparametric mapping were calculated via LORETA. Alpha power increased from baseline to post-session interval in the both age groups, indicating use-dependent plasticity. The anterior-posterior gradient (posterior>anterior) of alpha power increases from baseline to post-session interval in the left hemisphere was more pronounced in younger adults, than in older. Use-dependent plasticity has the same pattern of age differences as PASA postulates, that is, decrease in posterior coupled with increase in anterior areas. The results emphasize that PASA model reflects a global age-associated shift in brain function.

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Mechanisms of ischemic kidney tolerance in young and senescence-accelerated rats exposured to ischemic preconditioning or calorie restriction

Egor Plotnikov1, Nadezda Andrianova2, Stanislovas Jankauskas3, Irina Pevzner4, Ljubava Zorova5, Vasily Popkov6, Denis Silachev7, Natalia Kolosova8, Dmitry Zorov91A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, plotnikov@belozersky.msu.ru2A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, andnadya12@gmail.com3A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, jankauskas.ss@gmail.com4A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, irinapevzner@mail.ru5A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, lju_2003@list.ru6A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, popkov.vas@gmail.com7A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, silachev_dn@belozersky.msu.ru8Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), kolosova@bionet.nsc.ru9A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, zorov@belozersky.msu.ru Dietary restriction and ischemic preconditioning are the most efficient approaches ameliorating the severity of different pathological conditions. We investigated the protective potential of long-term calorie restriction and short ischemic preconditioning protocol in the model of acute kidney injury (AKI) in young Wistar and OXYS rats. In young rats, ischemic preconditioning, which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However, 6-month-old OXYS rats having signs of premature aging lost their ability to protect the ischemic kidney by IPC. However, CR of OXYS rats led to a significant decrease in creatinine and BUN levels after kidney ischemia, indicating significant protection.

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Material for regular publication

Evgeniya Privodnova1, Nina Volf2, Ekaterina Merculova3, Victoriya Bilik41Scientific Research Institute of Physiology and Basic Medicine, privodnovaeu@physiol.ru2Scientific Research Institute of Physiology and Basic Medicine, volf@physiol.ru3Scientific Research Institute of Physiology and Basic Medicine, merkaterine@gmail.com4Scientific Research Institute of Physiology and Basic Medicine, v.bilik@mail.ru Enter the abstract annotation ONLY hereMaterial for regular publication

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