MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE
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Browsing MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE by Subject "Alzheimer’s disease"
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Item Open Access CRITICAL ROLE OF BRAIN-SPECIFIC GANGLIOSIDES IN THE PATHOGENESIS OF TRAUMATIC BRAIN INJURY AND ALZHEIMER’S DISEASE(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Ponomarev, Eugene D.Major brain glycosphingolipids, also called brain gangliosides, are localized within neuronal lipid rafts (NLR) of neuronal axons and synapses and their role in neurodegenerative diseases remains unknown. Here, we compared the outcome of traumatic brain injury (TBI) and Alzheimer’s disease (AD) pathology in wild-type and glycosphingolipid-deficient animals. The St3gal5 gene encodes for ST3 β-galactoside alpha-2, 3-sialyltransferase 5, which is responsible for the biosynthesis of complex a- and b- and c- series gangliosides in the brain. We found that uninjured st3gal5-deficient mice exhibit normal cognitive and social behaviors, but do exhibit some very mild motor deficits. After TBI, st3gal5-deficient animals exhibit marked deficits in cognitive and motor functions, which was associated with increased hemorrhage and neuronal damage owing to the failure of NLR-induced platelet activation and serotonin (5-HT) secretion. The decrease in NLR-induced platelet-derived platelet activating factor (PAF) release also resulted in reduced microglial activation and central nervous system macrophage infiltration in the st3gal5-deficient animals after TBI. Further investigation demonstrated that the interaction of platelets with NLR stimulated neurite growth, increased the number of dendritic spines, and increased neuronal activity during TBI. To understand the role of gangliosides in Alzheimer’s disease pathology we crossed st3gal5-deficient mice with 5XFAD transgenic mice that overexpress three mutant human amyloid proteins AP695 and two presenilin PS1genes. We found that st3gal5-deficient 5XFAD mice had a significantly reduced burden of amyloid depositions, low level of neuroinflammation, and did not exhibit neuronal loss or synaptic dysfunction as compared to wild-type 5XFAD mice. St3gal5-deficient 5XFAD mice also performed significantly better in a cognitive test than wild-type 5XFAD control group. Finally, the treatment of wild-type 5XFAD mice with the sialic acid-specific Limax flavus lectin resulted in substantial improvement of AD pathology. Thus, our study establishes an important role for major brain glycolipids in the regulation of neuroinflammation, neuronal plasticity, synaptic functions and cognitive ability after a neuronal injury during TBI- and AD-related neurodegeneration.Item Open Access GUT MICROBIOME ALTERATIONS IN SENIORS SUFFERING FROM ALZHEIMER’S DISEASE(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Askarova, Sholpan; Kaiyrlykyzy, Aiym; Kozhakhmetov, Samat S.; Nurgaziyev, Madiyar; Kushugulova, Almagul R.Introduction: One of the important factors influencing human health and attracting increasing attention of scientists during the last two decades is gut microbiome. It has been demonstrated that the links exist between gut microbiome density and composition and a number of pathological conditions including diabetes, obesity and cardiovascular diseases. These diseases, in turn, are the established risk factors for the development of Alzheimer’s disease (AD). Moreover, there is data indicating that gut microbiome can directly affect brain functions. However, only few studies have characterized the human gut microbiome communities associated with AD. Therefore, more research is needed in order to reveal the relationships existing between gut microbiome and brain functions and their influence on the development and progression of AD. Material and methods: Stool samples were obtained from patients with AD (n =11) and cognitively normal age- and sex-matched participants (n =13). The composition of gut microbiome was characterized by 16S ribosomal RNA MiSeq sequencing. Data analysis was performed using an independent computational pipeline, less OTUs scripts (LotuS) [Hildebrand, F., 2013], SILVA reference database were used as reference for 16S rRNA alignment. Statistical analyses were performed using R version 3.0.2. Results: Our preliminary results demonstrated that gut microbiota of AD individuals had overall higher α-diversity compared to healthy controls, although this difference was not significant, while β-diversity analysis has revealed statistical significance (R-squared: 0.075975; p-value <0.033). Among bacterial genera, microbiome of AD participants was characterized by a preponderance of Eubacterium copros, Lachnospiraceae NK, Rikenellaceae RC9, Christensenellacea, Prevotella, Ruminococcus torgue, Parabacterides, Coprococcus and Corynebacterium (LDA score [log10] > 3), whereas the healthy microbiome was characterized by a preponderance of Lactobacillus, Holdemania, Holdemanella, Granucatella (LDA score [log10] > 3). The relative abundances of Lachnospiraceae, Lactobacillus, Eubacterium, and Odoribacter were significantly different in AD patients compared to healthy participants (p < 0.01). Our data are consistent with the results of Vogt et al. (2017) showing that in patients with AD the dominant families were Lachnospiraceae and Ruminococcaceae. Conclusion: Distinct microbial communities were associated with patients with AD when compared with cognitively healthy seniors. However, more data is needed to ascertain our findings.Item Open Access MRI-BASED STUDY OF VARIOUS COGNITIVE IMPAIRMENTS: CROSS-SECTIONAL STUDY(International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana, 2020) Kossumov, Alibek; Supiyev, AdilIntroduction: Clinical and diagnostic criteria for cognitive impairments are based neurophysiological tests or the presence of a history of vascular disease and stroke following the MRI scan. Materials and methods: The clinical data of 497 respondents collected in the form of standardized questionnaires and protocol, MRI data were examined. Respondents were divided by age groups (50- 54, 55-59, 60-64, 65-69, 70-75) with approximately the same sex ratio in each group. Cognitive function was evaluated according to the results of neurophysiological tests. Verbal memory was evaluated by reminding a list of 10 nouns. Immediate recall was evaluated using correctly recalled words summarized over 3 consecutive 1-minute trials (range 0-30). Delayed feedback was evaluated after the interval during which other cognitive tests were introduced (range 0-10). Fluency was assessed by the number of animals named by the respondents within 1minute. To assess attention, mental speed and concentration, participants were instructed to cross out two target letters embedded in a random letter grid, as quickly and accurately as possible, within 1minute (range 0-65). Brain MRI was performed with cognitive test. Results: When analyzing the assessment of verbal memory (range 0-30), the gradient of memory decline after 59 years per 1word was clearly expressed. The analysis of verbal fluency and the assessment of attention and concentration also showed a decrease in memory (1-2words less in each subsequent age group). According to the results of the final stage of testing, there was a tendency to decrease in the activity of long-term memory of both sexes with increasing age (more in men than in women). According to the MRI results, the respondents with the lowest cognitive function test results showed a picture of white matter lesion in the form of multiple foci of ischemia and local postischemic nodules, which might indicate the progression of dementia. Conclusion: According to the results of the study, a correlation was revealed, with increasing age, the concentration of attention, memory decreases and cognitive impairment develops due to damage to the white matter of the brain due to ischemia, which can lead to dementia and Alzheimer’s disease.