Upregulation of presynaptic mGluR2, but not mGluR3 in the epileptic medial perforant path

Judith Rohde, Timo Kirschstein, Wiebke Wilkars, Lorenz Müller, Tursonjan Tokay, Katrin Porath, Roland A. Bender, Rüdiger Köhling

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9 Citations (Scopus)

Abstract

Presynaptic metabotropic glutamate receptors (mGluRs) at glutamatergic synapses play a major role in governing release probability. Previous reports indicated a downregulation of group III mGluRs at the lateral perforant path-granule cell synapse in the chronically epileptic hippocampus. Here, we investigated the mGluR-dependent presynaptic inhibition at the medial perforant path-granule cell synapse in the pilocarpine-treated chronically epileptic rat. The specific group II mGluR agonist (2S,2′R,3′R)-2-(2′, 3′-dicarboxycyclopropyl)glycine (DCG-IV, 10 μM) significantly depressed medial perforant path-evoked responses in control slices, but significantly more so in epileptic tissue. This depression was accompanied by a significant increase of the paired-pulse ratio in both animal groups indicating a presynaptic mechanism. Moreover, we also found that this significantly enhanced DCG-IV effect in the medial perforant path recorded in slices from pilocarpine-treated rats was due to a significant increase of mGluR2, but not mGluR3 transcripts in the entorhinal cortex using quantitative real-time reverse transcriptase-PCR. Immunohistochemistry confirmed the increased expression of group II mGluRs in the epileptic medial molecular layer. These results demonstrate that chronic epilepsy not only causes downregulation of mGluRs in the hippocampus, but may also lead to enhanced expression of these receptors - at least in the medial perforant path.

Original languageEnglish
Pages (from-to)1867-1873
Number of pages7
JournalNeuropharmacology
Volume62
Issue number4
DOIs
Publication statusPublished - Mar 1 2012

Keywords

  • DCG-IV
  • Metabotropic glutamate receptor
  • Presynaptic inhibition

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Rohde, J., Kirschstein, T., Wilkars, W., Müller, L., Tokay, T., Porath, K., Bender, R. A., & Köhling, R. (2012). Upregulation of presynaptic mGluR2, but not mGluR3 in the epileptic medial perforant path. Neuropharmacology, 62(4), 1867-1873. https://doi.org/10.1016/j.neuropharm.2011.12.012