KFU. Card publication. Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of mammalian neuromuscular synapses

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PRENATAL HYPERHOMOCYSTEINEMIA INDUCES OXIDATIVE STRESS AND ACCELERATES 'AGING' OF MAMMALIAN NEUROMUSCULAR SYNAPSES

Form of presentation

Articles in international journals and collections

Year of publication

2019

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Authors, employees of KFU

Bukharaeva Ellya Akhmetovna, author

Giniatullin Rashid Askhatovich, author

Ziyatdinova Guzel Kamilevna, author

Sitdikova Guzel Faritovna, author

Khaertdinov Nail Nazimovich, author

Khuzakhmetova Venera Faritovna, author

Yakovlev Aleksey Valerevich, author

Yakovleva Olga Vladislavovna, author

Bibliographic description in the original language

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.

Annotation

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.

Keywords

homocysteine, hyperhomocysteinemia, oxidative stress, release in synapses

The name of the journal

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

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=202467&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Bukharaeva Ellya Akhmetovna	ru_RU
dc.contributor.author	Giniatullin Rashid Askhatovich	ru_RU
dc.contributor.author	Ziyatdinova Guzel Kamilevna	ru_RU
dc.contributor.author	Sitdikova Guzel Faritovna	ru_RU
dc.contributor.author	Khaertdinov Nail Nazimovich	ru_RU
dc.contributor.author	Khuzakhmetova Venera Faritovna	ru_RU
dc.contributor.author	Yakovlev Aleksey Valerevich	ru_RU
dc.contributor.author	Yakovleva Olga Vladislavovna	ru_RU
dc.date.accessioned	2019-01-01T00:00:00Z	ru_RU
dc.date.available	2019-01-01T00:00:00Z	ru_RU
dc.date.issued	2019	ru_RU
dc.identifier.citation	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.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=202467&p_lang=2	ru_RU
dc.description.abstract	INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE	ru_RU
dc.description.abstract	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.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject	homocysteine	ru_RU
dc.subject	hyperhomocysteinemia	ru_RU
dc.subject	oxidative stress	ru_RU
dc.subject	release in synapses	ru_RU
dc.title	Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of mammalian neuromuscular synapses	ru_RU
dc.type	Articles in international journals and collections	ru_RU