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Status epilepticus impairs synaptic plasticity in rat hippocampus and is followed by changes in expression of NMDA receptors

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Abstract

Cognitive deficits and memory loss are frequent in patients with temporal lobe epilepsy. Persistent changes in synaptic efficacy are considered as a cellular substrate underlying memory processes. Electrophysiological studies have shown that the properties of short-term and long-term synaptic plasticity in the cortex and hippocampus may undergo substantial changes after seizures. However, the neural mechanisms responsible for these changes are not clear. In this study, we investigated the properties of short-term and long-term synaptic plasticity in rat hippocampal slices 24 h after pentylenetetrazole (PTZ)-induced status epilepticus. We found that the induction of long-term potentiation (LTP) in CA1 pyramidal cells is reduced compared to the control, while short-term facilitation is increased. The experimental results do not support the hypothesis that status epilepticus leads to background potentiation of hippocampal synapses and further LTP induction becomes weaker due to occlusion, as the dependence of synaptic responses on the strength of input stimulation was not different in the control and experimental animals. The decrease in LTP can be caused by impairment of molecular mechanisms of neuronal plasticity, including those associated with NMDA receptors and/or changes in their subunit composition. Realtime PCR demonstrated significant increases in the expression of GluN1 and GluN2A subunits 3 h after PTZ-induced status epilepticus. The overexpression of obligate GluN1 subunit suggests an increase in the total number of NMDA receptors in the hippocampus. A 3-fold increase in the expression of the GluN2B subunit observed 24 h after PTZ-induced status epilepticus might be indicative of an increase in the proportion of GluN2B-containing NMDA receptors. Increased expression of the GluN2B subunit may be a cause for reducing the magnitude of LTP at hippocampal synapses after status epilepticus.

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Abbreviations

ACSF:

artificial cerebrospinal fluid

CycA:

cyclophilin A

fEPSP:

field excitatory postsynaptic potentials

LTP:

long-term synaptic potentiation

NMDA:

N-methyl-Daspartate

PTZ:

pentylenetetrazole

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    T. Y. Postnikova, O. E. Zubareva, K. K. Kim, L. G. Magazanik & A. V. Zaitsev

  2. Peter the Great St. Petersburg Polytechnic University, 195251, St. Petersburg, Russia

    T. Y. Postnikova

  3. Institute of Experimental Medicine, 197376, St. Petersburg, Russia

    O. E. Zubareva & A. A. Kovalenko

  4. Saint Petersburg State University, 199034, St. Petersburg, Russia

    L. G. Magazanik

Authors
  1. T. Y. Postnikova
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  2. O. E. Zubareva
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  3. A. A. Kovalenko
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  4. K. K. Kim
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  5. L. G. Magazanik
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  6. A. V. Zaitsev
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Correspondence to A. V. Zaitsev.

Additional information

Original Russian Text © T. Y. Postnikova, O. E. Zubareva, A. A. Kovalenko, K. K. Kim, L. G. Magazanik, A. V. Zaitsev, 2017, published in Biokhimiya, 2017, Vol. 82, No. 3, pp. 418-428.

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Postnikova, T.Y., Zubareva, O.E., Kovalenko, A.A. et al. Status epilepticus impairs synaptic plasticity in rat hippocampus and is followed by changes in expression of NMDA receptors. Biochemistry Moscow 82, 282–290 (2017). https://doi.org/10.1134/S0006297917030063

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  • DOI: https://doi.org/10.1134/S0006297917030063

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