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Published on: November 20, 2015
Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats
A V Yakovlev1, E Kurmashova1, E Gataulina1
1Department of Human and Animal Physiology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kremlevskaya str 18, Kazan 420008, Russia.
Insights
Prenatal exposure to high homocysteine (hHCy) in rats increases seizure susceptibility and severity. This is linked to an altered excitation/inhibition balance in the brain, potentially explaining the epilepsy risk associated with hHCy.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Epilepsy Research
Background:
- Neonatal seizures can lead to lasting neurological damage.
- Elevated homocysteine (hHCy) levels are linked to epilepsy.
- The impact of prenatal hHCy on neonatal seizure susceptibility is not well understood.
Purpose of the Study:
- To investigate the effect of prenatal hyperhomocysteinemia (hHCy) on seizure susceptibility in neonatal rats.
- To analyze the underlying neurophysiological mechanisms, including excitation/inhibition balance and GABAergic function.
Main Methods:
- Prenatal hHCy induced via maternal high-methionine diet.
- Seizure susceptibility assessed using flurothyl-induced seizures in pups (postnatal weeks 1-3).
- Hippocampal electrophysiology used to record neuronal activity and analyze GABAergic function.
Main Results:
- hHCy rats exhibited increased seizure severity and shorter latency.
- Electrophysiology revealed higher neuronal activity and enhanced seizure-like events in hHCy rats.
- An increased glutamate/GABA ratio and altered GABA reversal potential were observed, indicating a shift towards excitation.
Conclusions:
- Prenatal hHCy increases neonatal seizure susceptibility in rats.
- This heightened susceptibility is associated with a shift in the brain's excitation/inhibition balance towards excitation.
- Findings support the clinical association between hHCy and increased epilepsy risk.
Aims:
Neonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine - hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy.
Main Methods:
Prenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed.
Key Findings:
Rats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats.
Significance:
The higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.
