Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats

Yakovlev, A. V.; Kurmashova, E.; Gataulina, E.; Gerasimova, E.; Khalilov, Ilgam; Ситдикова, Г. Ф.

doi:10.1016/j.lfs.2023.121953

Cited by 3 publications

(2 citation statements)

References 86 publications

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“…The higher excitability of TG afferents in rats with hHCY was further supported by a higher baseline activity of the TG nerve, which is also similar to previous findings in the hippocampus and somatosensory cortex of rats with prenatal hHCY 30,62 . Cluster analysis of APs was used to assess indirectly the activity of nerve fibers of different types according to Zakharov et al 38 .…”

Section: Discussionsupporting

confidence: 82%

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Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia

Ermakova,

Shaidullova,

Gafurov

et al. 2024

Headache

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ObjectivesInvestigation of chronic homocysteine action on the excitability and N‐methyl‐D‐aspartate (NMDA) sensitivity of the peripheral trigeminovascular system of rats.BackgroundMigraine is a neurological disease that affects 15%–20% of the general population. Epidemiological observations show that an increase of the sulfur‐containing amino acid homocysteine in plasma—called hyperhomocysteinemia—is associated with a high risk of migraine, especially migraine with aura. In animal studies, rats with hyperhomocysteinemia demonstrated mechanical allodynia, photophobia, and anxiety, and higher sensitivity to cortical spreading depression. In addition, rats with hyperhomocysteinemia were more sensitive in a model of chronic migraine induced by nitroglycerin which indicated the involvement of peripheral nociceptive mechanisms. The present work aimed to analyze the excitability of meningeal afferents and neurons isolated from the trigeminal ganglion of rats with prenatal hyperhomocysteinemia.MethodsExperiments were performed on male rats born from females fed with a methionine‐rich diet before and during pregnancy. The activity of meningeal afferents was recorded extracellularly in hemiskull preparations ex vivo and action potentials were characterized using cluster analysis. The excitability of trigeminal ganglion neurons was assessed using whole‐cell patch clamp recording techniques and calcium imaging studies. Meningeal mast cells were stained using toluidine blue.ResultsThe baseline extracellular recorded electrical activity of the trigeminal nerve was higher in the hyperhomocysteinemia group with larger amplitude action potentials. Lower concentrations of KCl caused an increase in the frequency of action potentials of trigeminal afferents recorded in rat hemiskull ex vivo preparations. In trigeminal ganglion neurons of rats with hyperhomocysteinemia, the current required to elicit at least one action potential (rheobase) was lower, and more action potentials were induced in response to stimulus of 2 × rheobase. In controls, short‐term application of homocysteine and its derivatives increased the frequency of action potentials of the trigeminal nerve and induced Ca2+ transients in neurons, which are associated with the activation of NMDA receptors. At the same time, in rats with hyperhomocysteinemia, we did not observe an increased response of the trigeminal nerve to NMDA. Similarly, the parameters of Ca2+ transients induced by NMDA, homocysteine, and its derivatives were not changed in rats with hyperhomocysteinemia. Acute incubation of the meninges in homocysteine and homocysteinic acid did not change the state of the mast cells, whereas in the model of hyperhomocysteinemia, an increased degranulation of mast cells in the meninges was observed.ConclusionsOur results demonstrated higher excitability of the trigeminal system of rats with hyperhomocysteinemia. Together with our previous finding about the lower threshold of generation of cortical spreading depression in rats with hyperhomocysteinemia, the present data provide evidence of homocysteine as a factor that increases the sensitivity of the peripheral migraine mechanisms, and the control of homocysteine level may be an important strategy for reducing the risk and/or severity of migraine headache attacks.

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Section: Discussionsupporting

confidence: 82%

“…30,62 Cluster analysis of APs was used to assess indirectly the activity of nerve fibers of different types according to Zakharov et al38 The ner-Generation of action potentials in TG neurons from the naive and hHCY groups. (A) The original recordings of APs in response to a threshold stimulus (rheobase).…”

mentioning

confidence: 99%

Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia

Ermakova,

Shaidullova,

Gafurov

et al. 2024

Headache

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H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia

Yakovlev,

Detterer,

Yakovleva

et al. 2024

Journal of Pharmacological Sciences

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Evaluation of sensomotor development, behavioral reactions and cognitive functions of the second generation of rats with hyperhomocysteinemia

Yakovleva,

Skripnikova,

Yakovlev

et al. 2024

Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova

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The adverse maternal exposure during pregnancy leads to developmental disorders in the offspring that can be passed on to later generations. Epigenetic regulation of DNA transcription may mediate inherited metabolic diseases. An increase in homocysteine concentration in the blood is associated with epigenetic modifications of the genome, which can alter the fetal brain’s development program and cause cognitive impairment. The aim of our work was to identify changes in sensomotor development, behavioral reactions and cognitive functions of offspring of second generation rats (HcyF2) of hyperhomocysteinemia. Our results indicate that unconditioned reflexes and physical parameters are delayed in HcyF2 rats. In “open field”, HcyF2 rats showed higher levels of anxiety and decreased exploratory and motor activity, while coordination of movements studied in “rotarod” test was not impaired. Decreased limb muscle strength was shown in the “grip strength” test. Additionally, HcyF2 rats demonstrated an impaired learning and longterm memory in the Morris water maze. Biochemical analysis revealed an imbalance in the antioxidant systems, which was attributed to decreased activity of glutathione peroxidases and H2S synthesis enzymes. It was suggested that elevated homocysteine levels during pregnancy may result in epigenetic modifications of the genome, which can impact the metabolism of offspring and be inherited by future generations.

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Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats

Cited by 3 publications

References 86 publications

Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia

Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia

H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia

Evaluation of sensomotor development, behavioral reactions and cognitive functions of the second generation of rats with hyperhomocysteinemia

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