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Up‐regulation of the metabotropic glutamate receptor mGluR4 in hippocampal neurons with reduced seizure vulnerability
Author(s) -
Lie Ailing A.,
Becker Albert,
Behle Karsten,
Beck Heinz,
Malitschek Barbara,
Conn P. Jeffrey,
Kuhn Rainer,
Nitsch Robert,
Plaschke Martina,
Schramm Johannes,
Elger Christian E.,
Wiestler Otmar D.,
Blümcke Ingmar
Publication year - 2000
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(200001)47:1<26::aid-ana7>3.0.co;2-p
Subject(s) - hippocampal formation , dentate gyrus , epileptogenesis , neuroscience , granule cell , glutamate receptor , metabotropic receptor , biology , metabotropic glutamate receptor , epilepsy , receptor , biochemistry
Selective hippocampal cell loss and altered neurotransmitter receptor expression have been proposed as pathogenic mechanisms in the development of chronic mesial temporal lobe epilepsy (TLE). Studies in animal models point to metabotropic glutamate receptors (mGluRs) as modulators of hippocampal epileptogenesis. In addition, mGluRs may constitute specific targets for the development of novel anticonvulsive drugs. As mGluR4 represents an inhibitory class III mGluR associated with the reduction of intracellular cyclic AMP levels and calcium influx, we have analyzed the regional and cellular expression of mGluR4 in surgical hippocampal specimens obtained from patients with TLE by using immunohistochemistry and in situ hybridization. Although the hippocampi of control specimens (n = 11) were almost devoid of mGluR4 immunolabeling, all TLE specimens (n = 35) showed a striking up‐regulation of mGluR4 immunoreactivity, in particular within the dentate gyrus. Immunoelectron microscopy localized the receptor protein to the periphery of presynaptic and postsynaptic membranes. In situ hybridization revealed increased transcript levels of mGluR4 in dentate granule cells and residual CA4 neurons of TLE specimens compared with controls. Our results suggest a potential role of mGluR4 in counteracting excitatory hippocampal activity and in modulating seizure‐associated vulnerability of hippocampal neurons. These data may also provide a basis for pharmacological studies of mGluR4 agonists as potential novel drugs in the treatment of TLE. Ann Neurol 2000; 47:26–35