Immunization against specific fragments of neurotrophin p75 receptor protects forebrain cholinergic neurons in the olfactory bulbectomized mice

Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with marked cholinergic neuron loss and amyloid-β (Aβ) peptide accumulation in the brain. The cytotoxicity in AD is mediated, at least in part, by Aβ binding with the extracellular domain of the p75 neurotrophin receptor (p75NTR), localized predominantly in the membranes of acetylcholine-producing neurons in the basal forebrain. Hypothesizing that an open unstructured loop of p75NTR might be the effective site for Aβ binding, we have immunized both olfactory bulbectomized (OBX) and sham-operated (SO) mice (n = 82 and 49, respectively) with synthetic peptides, structurally similar to different parts of the loops, aiming to block them by specific antibodies. OBX-mice have been shown in previous studies, and confirmed in the present one, to be characterized by typical behavioral, morphological and biochemical AD hallmarks, including cholinergic deficits in forebrain neurons. Immunization of OBX- or SO-mice with KLH conjugated fragments of p75NTR induced high titers of specific serum antibodies for each of nine chosen fragments. However, maximal protective effects on spatial memory, evaluated in a Morris water maze, and on activity of choline acetyltransferase in forebrain neurons, detected by immunoreactivity to specific antibodies, were revealed only for peptides with amino acid residue sequences of 155-164 and 167-176. We conclude that the approach based on immunological blockade of specific p75NTR sites, linked with the cytotoxicity, is a useful and effective tool for study of AD-associated mechanisms and for development of highly selective therapy of cholinergic malfunctioning in AD patient

Deoxygenation affects composition of membrane-bound proteins in human erythrocytes

Background/Aims: ATP release from erythrocyte plays a key role in hypoxia-induced elevation of blood flow in systematic circulation. We have previously shown that hemolysis contributes to erythrocyte ATP release triggered by several stimuli, including hypoxia, but the molecular mechanisms of hypoxia-increased membrane fragility remain unknown. Methods: In this study, we compared the action of hypoxia on hemolysis, ATP release and the composition of membrane-bound proteins in human erythrocytes. Results: Twenty minutes incubation of human erythrocytes in the oxygen-free environment increased the content of extracellular hemoglobin by ∼1.5 fold. Paired measurements of hemoglobin and ATP content in the same samples, showed a positive correlation between hemolysis and ATP release. Comparative analysis of SDS-PAGE electrophoresis of erythrocyte ghosts obtained under control and deoxygenated conditions revealed a ∼2-fold elevation of the content of membrane-bound protein with Mr of ∼60 kDa. Conclusion: Deoxygenation of human erythrocytes affects composition of membrane-bound proteins. Additional experiments should be performed to identify the molecular origin of 60 kDa protein and its role in the attenuation of erythrocyte integrity and ATP release in hypoxic conditions

Loss of midbrain dopamine neurons and altered apomorphine EEG effects in the 5xFAD mouse model of Alzheimer's disease

Cognitive malfunction, synaptic dysfunction, and disconnections in neural networks are core deficits in Alzheimer's disease (AD). 5xFAD mice, a transgenic model of AD, are characterized by an enhanced level of amyloid-β and abnormal neurotransmission. The dopaminergic (DA) system has been shown to be involved in amyloid-β transformations and neuronal plasticity; however, its role in functional network changes in familial AD still remains unclear. In 5xFAD and non-transgenic freely moving mice, electroencephalograms (EEGs) were simultaneously recorded from the secondary motor cortex (MC), superficial layers of the hippocampal CA1 area (HPC), substantia nigra (SN), and ventral tegmental area (VTA). EEGs and their frequency spectra were analyzed before and after systemic injection of a DA receptor agonist, apomorphine (APO). In the baseline EEG from MC and HPC of 5xFAD mice, delta and alpha oscillations were enhanced and beta activity was attenuated, compared to control mice. In VTA and SN of 5xFAD mice, delta-theta activity was decreased and beta oscillations dominated. In control mice, APO suppressed delta activity in VTA to a higher extent than in MC, whereas in 5xFAD mice, this difference was eliminated due to attenuation of the delta suppression in VTA. APO increased beta activity in MC of mice from both groups while significant beta suppression was observed in VTA of 5xFAD mice. These mice were characterized by significant decrease of tyrosine hydroxylase immunopositive cells in both VTA and SN and of DA transporter in MC and hippocampal dentate gyrus. We suggest that the EEG modifications observed in 5xFAD mice are associated with alterations in dopaminergic transmission, resulting in adaptive changes in the cerebral networks in the course of familial AD development

Histopathological characterization of skeletal muscle during postnatal ontogenesis of dysferlin-deficient mice

57-5

Половое развитие подростков в Томской области

Background. Sexual development of adolescents is one of the important indicators of the population well-being, the study of which, in the context of the world trend towards a change in the period of puberty, can contribute to the identification of public health problems. Objective. Our aim was to study the basic indicators of sexual development of adolescents and to determine the regional characteristics of this population. Methods. The evaluation of secondary sexual characteristics was carried out by specialists according to Tanner criteria. Ultrasound examination of organs of the reproductive system was carried out using a portable scanner Mindray M7. The analysis of the results was carried out taking into account the gender, living conditions, physical development. Results. We examined 7,120 adolescents aged from 13 to 16 years. The degree of axillary hair distribution by Tanner criteria was 2.4±0.7 in young men, 2.9±0.4 — in girls, pubic hair — 2.0±0.9 and 2.6±0.8, respectively. The indicator of development of mammary glands by Tanner criteria in girls was 2.6±0.8, menstrual function by Tanner criteria — 2.4±0.8. Herewith, urban adolescents had later terms of appearance of the secondary sexual characteristics in comparison with the inhabitants of rural areas. Conclusion. We registered the delayed sexual development in 8.1% of girls and 13.6% of young men. Urban youths have experienced a delay in gonadal growth. Among the female population there was an outstripping growth and development of the uterus and ovaries in comparison with rural adolescents. Половое развитие подростков — один из важных показателей благополучия населения, изучение которого в условиях мировой тенденции к изменению сроков наступления пубертатного периода может способствовать выявлению проблем общественного здравоохранения. Цель исследования — изучить основные показатели полового развития подростков и определить региональные особенности данной популяции. Методы. Оценка вторичных половых признаков проводилась врачами-специалистами по критериям Tanner. Ультразвуковое исследование органов репродуктивной системы осуществлялось при помощи переносного сканера Mindray M7. Анализ результатов проводили с учетом пола, условий проживания, физического развития. Результаты. Обследовано 7120 подростков в возрасте от 13 до 16 лет. Степень оволосения подмышечной впадины по критериям Tanner составила у юношей 2,4±0,7, у девушек — 2,9±0,4, степень лобкового оволосения — 2,0±0,9 и 2,6±0,8 соответственно. Показатель развития молочных желез по критериям Tanner у девушек составил 2,6±0,8, менструальная функция по критериям Tanner — 2,4±0,8. При этом у городских подростков выявлены более поздние сроки появления вторичных половых признаков в сравнении с жителями сельских районов. Заключение. У 8,1% девушек и 13,6% юношей зарегистрирована задержка полового развития. У городских юношей выявлена задержка роста гонад; среди женского населения наблюдалось опережение роста и развития матки и яичников в сравнении с сельскими подростками.