PMID- 30946975
OWN - NLM
STAT- MEDLINE
DCOM- 20191218
LR  - 20200106
IS  - 1873-474X (Electronic)
IS  - 0736-5748 (Linking)
VI  - 75
DP  - 2019 Jun
TI  - Prenatal hyperhomocysteinemia induces oxidative stress and accelerates 'aging' of 
      mammalian neuromuscular synapses.
PG  - 1-12
LID - S0736-5748(18)30302-2 [pii]
LID - 10.1016/j.ijdevneu.2019.03.004 [doi]
AB  - 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.
CI  - Copyright (c) 2019 ISDN. Published by Elsevier Ltd. All rights reserved.
FAU - Khuzakhmetova, Venera
AU  - Khuzakhmetova V
AD  - Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of 
      RAS, Kazan, Russia; Kazan Federal University, Kazan, Russia.
FAU - Yakovleva, Olga
AU  - Yakovleva O
AD  - Kazan Federal University, Kazan, Russia.
FAU - Dmitrieva, Svetlana
AU  - Dmitrieva S
AD  - Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of 
      RAS, Kazan, Russia.
FAU - Khaertdinov, Nail
AU  - Khaertdinov N
AD  - Kazan Federal University, Kazan, Russia.
FAU - Ziyatdinova, Guzel
AU  - Ziyatdinova G
AD  - Kazan Federal University, Kazan, Russia.
FAU - Giniatullin, Rashid
AU  - Giniatullin R
AD  - Kazan Federal University, Kazan, Russia; A.I. Virtanen Institute, University of 
      Eastern Finland, Kuopio, Finland.
FAU - Yakovlev, Aleksey
AU  - Yakovlev A
AD  - Kazan Federal University, Kazan, Russia.
FAU - Bukharaeva, Ellya
AU  - Bukharaeva E
AD  - Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of 
      RAS, Kazan, Russia; Kazan Federal University, Kazan, Russia.
FAU - Sitdikova, Guzel
AU  - Sitdikova G
AD  - Kazan Federal University, Kazan, Russia. Electronic address: 
      sitdikovaguzel@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190401
PL  - United States
TA  - Int J Dev Neurosci
JT  - International journal of developmental neuroscience : the official journal of the 
      International Society for Developmental Neuroscience
JID - 8401784
RN  - 0 (Oxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Female
MH  - Hydrogen Peroxide/pharmacology
MH  - Hyperhomocysteinemia/*metabolism
MH  - Lipid Peroxidation/physiology
MH  - Motor Neurons/metabolism
MH  - Muscle Strength/physiology
MH  - Muscle, Skeletal/*metabolism
MH  - Neuromuscular Junction/drug effects/*physiology
MH  - Oxidants/pharmacology
MH  - Oxidative Stress/drug effects/*physiology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Synaptic Transmission/drug effects/*physiology
OTO - NOTNLM
OT  - Developing neuromuscular junction
OT  - Kinetic of quantum release
OT  - Muscle strength
OT  - Neonatal and adult rats
OT  - Oxidative stress
OT  - Prenatal hyperhomocysteinemia
OT  - Spontaneous and evoked release
EDAT- 2019/04/05 06:00
MHDA- 2019/12/19 06:00
CRDT- 2019/04/05 06:00
PHST- 2018/10/19 00:00 [received]
PHST- 2019/02/06 00:00 [revised]
PHST- 2019/03/21 00:00 [accepted]
PHST- 2019/04/05 06:00 [pubmed]
PHST- 2019/12/19 06:00 [medline]
PHST- 2019/04/05 06:00 [entrez]
AID - S0736-5748(18)30302-2 [pii]
AID - 10.1016/j.ijdevneu.2019.03.004 [doi]
PST - ppublish
SO  - Int J Dev Neurosci. 2019 Jun;75:1-12. doi: 10.1016/j.ijdevneu.2019.03.004. Epub 
      2019 Apr 1.