Казанский (Приволжский) федеральный университет, КФУ
КАЗАНСКИЙ
ФЕДЕРАЛЬНЫЙ УНИВЕРСИТЕТ
 
PRENATAL HYPERHOMOCYSTEINEMIA INDUCES OXIDATIVE STRESS AND ACCELERATES 'AGING' OF MAMMALIAN NEUROMUSCULAR SYNAPSES
Форма представленияСтатьи в зарубежных журналах и сборниках
Год публикации2019
Языканглийский
  • Бухараева Элля Ахметовна, автор
  • Гиниатуллин Рашид Асхатович, автор
  • Зиятдинова Гузель Камилевна, автор
  • Ситдикова Гузель Фаритовна, автор
  • Хаертдинов Наиль Назимович, автор
  • Хузахметова Венера Фаритовна, автор
  • Яковлев Алексей Валерьевич, автор
  • Яковлева Ольга Владиславовна, автор
  • Библиографическое описание на языке оригинала Khuzakhmetova V. F. Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of mammalian neuromuscular synapses / V. F. Khuzakhmetova, O. V. Yakovleva, S. A. Dmitrieva, N. N. Khaertdinov, G. K. Ziyatdinova, R. A. Giniatullin, A.V. Yakovlev, E. A. Bukharaeva, G. F. Sitdikova // International Journal of Developmental Neuroscience. - 2019.- Volume 75, P. 1-12.
    Аннотация Enhanced levels of homocysteine during pregnancy induce oxidative stress and contribute to many age-related diseases. In this study, we analyzed age-dependent synaptic modifications in developing neuromuscular synapses of rats with prenatal hyperhomocysteinemia (hHCY). One of the main findings indicate that the intensity and the timing of transmitter release in synapses of neonatal (P6 and P10) hHCY rats acquired features of matured synaptic transmission of adult rats. The amplitude and frequency of miniature end-plate currents (MEPCs) and evoked transmitter release were higher in neonatal hHCY animals compared to the control group. Analysis of the kinetics of neurotransmitter release demonstrated more synchronized release in neonatal rats with hHCY. At the same time lower release probability was observed in adults with hHCY. Spontaneous transmitter release in neonates with hHCY was inhibited by hydrogen peroxide (H 2 O 2 ) whereas in controls this oxidant was effective only in adult animals indicating a higher susceptibility of motor nerve terminals to oxidative stress. The morphology and the intensity of endocytosis of synaptic vesicles in motor nerve endings was assessed using the fluorescence dye FM 1-43. Adult-like synapses were found in neonates with hHCY which were characterized by a larger area of presynaptic terminals compared to controls. No difference in the intensity of FM 1-43 fluorescence was observed between two groups of animals. Prenatal hHCY resulted in reduced muscle strength assessed by the Paw Grip Endurance test. Using biochemical assays we found an increased level of H 2 O 2 and lipid peroxidation products in the diaphragm muscles of hHCY rats. This was associated with a lowered activity of superoxide dismutase and glutathione peroxidase. Our data indicate that prenatal hHCY induces oxidative stress and apparent faster functional and morphological “maturation” of motor synapses. Our results uncover synaptic mechanisms of disrupted muscle function observed in hHCY conditions which may contribute to the pathogenesis of motor neuronal diseases associated with enhanced level of homocysteine.
    Ключевые слова homocysteine, hyperhomocysteinemia, oxidative stress, release in synapses
    Название журнала INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
    URL https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063781081&doi=10.1016%2fj.ijdevneu.2019.03.004&partnerID=40&md5=21a3630444ebc79df7506457dbb506ed
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