Effects of Maternal Hyperhomocysteinemia on the Early Physical Development and Neurobehavioral Maturation of Rat Offspring

Gerasimova, E.; Yakovleva, O. V.; Burkhanova, Gulshat; Ziyatdinova, Guzel; Khaertdinov, N. N.; Ситдикова, Г. Ф.

doi:10.1007/s12668-016-0326-6

Cited by 16 publications

(16 citation statements)

References 15 publications

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“…In the present study we show how the transmitter release from the motor nerve endings, synapse morphology, muscle strength and redox status are modified in animals with prenatal hHCY. In our model of prenatal methionine‐based dietary hHCY the level of HCY is elevated not only in dams but also in their offspring suggesting an attractive approach to test the role of HCY in early development (Gerasimova et al, 2017; Yakovleva et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Pups for control experiments were born from females fed ad libitum with a control diet. Pups with prenatal hHCY were born from females which received daily methionine (7.7 g/kg body weight) with food starting three weeks prior to and during pregnancy (Gerasimova et al, 2017). The total HCY level in plasma was detected by voltammetry measurements of products of its reactions with о‐quinone (Lee et al, 2014; Gerasimova et al, 2017)…”

Section: Methodsmentioning

confidence: 99%

“…Elevated levels of HCY during pregnancy (prenatal hHCY) impair fetus development, resulted in functional disabilities, learning deficits and skeletal muscle myopathy of the offspring (Hague, 2003; Picker and Levy, 2010; Gerasimova et al, 2017; Makhro et al, 2008; Yakovlev et al, 2018; Yakovelva et al, 2018). Newborns are particularly vulnerable to oxidative stress due to high ability of ROS production and decreased antioxidant protection (Marseglia et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Recently it was shown that HCY sensitizes neuromuscular junction to the inhibitory effect of H 2 O 2 via activation of NMDA receptors and nitric oxide (Bukharaeva et al, 2015;Wang et al, 2018). Elevated levels of HCY during pregnancy (prenatal hHCY) impair fetus development, resulted in functional disabilities, learning deficits and skeletal muscle myopathy of the offspring (Hague, 2003;Picker and Levy, 2010;Gerasimova et al, 2017;Makhro et al, 2008;Yakovelva et al, 2018). Newborns are particularly vulnerable to oxidative stress due to high ability of ROS production and decreased antioxidant protection (Marseglia et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

Khuzakhmetova

Yakovleva

Dmitrieva

et al. 2019

Intl J of Devlp Neuroscience

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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 (H2O2) 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 H2O2 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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

Khuzakhmetova

Yakovleva

Dmitrieva

et al. 2019

Intl J of Devlp Neuroscience

Self Cite

View full text Add to dashboard Cite

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“…In fact, the expression of the H 2 S-producing enzymes CBS and 3-MST increases from the late embryonic to the early postnatal period (Enokido et al, 2005 ) highlighting the importance of this signaling pathway. Apart from the production of H 2 S, another important role of CBS may comprise a decrease of the neurotoxic aminoacid homocysteine level in early development (Rosenquist and Finnell, 2001 ; Gerasimova et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Age-Dependent, Subunit Specific Action of Hydrogen Sulfide on GluN1/2A and GluN1/2B NMDA Receptors

Yakovlev

Kurmasheva

Ishchenko

et al. 2017

Front. Cell. Neurosci.

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Hydrogen sulfide (H2S) is an endogenously produced neuroactive gas implicated in many key processes in the peripheral and central nervous system. Whereas the neuroprotective role of H2S has been shown in adult brain, the action of this messenger in newborns remains unclear. One of the known targets of H2S in the nervous system is the N-methyl-D-aspartate (NMDA) glutamate receptor which can be composed of different subunits with distinct functional properties. In the present study, using patch clamp technique, we compared the effects of the H2S donor sodium hydrosulfide (NaHS, 100 μM) on hippocampal NMDA receptor mediated currents in rats of the first and third postnatal weeks. This was supplemented by testing effects of NaHS on recombinant GluN1/2A and GluN1/2B NMDA receptors expressed in HEK293T cells. The main finding is that NaHS action on NMDA currents is age-dependent. Currents were reduced in newborns but increased in older juvenile rats. Consistent with an age-dependent switch in NMDA receptor composition, in HEK239T cells expressing GluN1/2A receptors, NaHS increased NMDA activated currents associated with acceleration of desensitization and decrease of the deactivation rate. In contrast, in GluN1/2B NMDA receptors, which are prevalent in newborns, NaHS decreased currents and reduced receptor deactivation without effect on the desensitization rate. Adenylate cyclase inhibitor MDL-12330A (10 μM) did not prevent the age-dependent effects of NaHS on NMDA evoked currents in pyramidal neurons of hippocampus. The reducing agent dithiothreitol (DTT, 2 mM) applied on HEK293T cells prevented facilitation induced by NaHS on GluN1/2A NMDA receptors, however in GluN1/2B NMDA receptors the inhibitory effect of NaHS was still observed. Our data indicate age-dependent effect of H2S on NMDA receptor mediated currents determined by glutamate receptor subunit composition. While the inhibitory action of H2 on GluN1/2B receptors could limit the excessive activation in early age, the enhanced functionality of GluN1/2A receptor in the presence of this gasotransmitter can enlarge synaptic efficacy and promote synaptic plasticity in adults.

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Effects of Homocysteine and its Derivatives on Spontaneous Network Activity in the Hippocampus of Neonatal Rat Pups

Kurmashova

Gataulina

Зефиров

et al. 2020

Neurosci Behav Physi

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Effects of Maternal Hyperhomocysteinemia on the Early Physical Development and Neurobehavioral Maturation of Rat Offspring

Cited by 16 publications

References 15 publications

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

Prenatal hyperhomocysteinemia induces oxidative stress and accelerates ‘aging’ of mammalian neuromuscular synapses

Age-Dependent, Subunit Specific Action of Hydrogen Sulfide on GluN1/2A and GluN1/2B NMDA Receptors

Effects of Homocysteine and its Derivatives on Spontaneous Network Activity in the Hippocampus of Neonatal Rat Pups

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