Upregulation of presynaptic mGluR2, but not mGluR3 in the epileptic medial perforant path.
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, 10μM) 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.
Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstrasse 9, 18057 Rostock, Germany.
Judith
J
Rohde
Timo
T
Kirschstein
Wiebke
W
Wilkars
Lorenz
L
Müller
Tursonjan
T
Tokay
Katrin
K
Porath
Roland A
RA
Bender
Rüdiger
R
Köhling
D000818:Animals; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019580:Perforant Pathway / Q000378:metabolism*; D010862:Pilocarpine; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015854:Up-Regulation
D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D010862:Pilocarpine