Abstract:
:Aberrant axonal reorganization and altered distribution of neurotransmitter receptor subtypes have been proposed as major pathogenic mechanisms for hippocampal hyperexcitability in chronic temporal lobe epilepsies (TLE). Recent data point to excitatory class I metabotropic glutamate receptors (mGluR1 and mGluR5) as interesting candidates. Here, we have analyzed the hippocampal distribution and mRNA expression of mGluR1 and mGluR5 in two rat models of limbic seizures, i.e. electrical kindling and intraperitoneal kainate injections, as well as in human TLE. Quantitative RT-PCR analysis detected a significant increase of hippocampal mGluR1 gene transcript levels in kainate treated and kindled rats. In addition, microdissected hippocampal tissue samples localized this increase to the dentate gyrus. Using immunohistochemistry with mGluR1alpha subtype specific antibodies, increased labeling was observed within the dentate gyrus molecular layer (DG-ML). A similar pattern of increased mGluR1alpha neuropil staining was found within the DG-ML of epilepsy patients (n = 42) compared with peritumoral hippocampus specimens obtained from nonepileptic patients (biopsy controls, n = 3). This increase was detected in TLE patients with segmental hippocampal cell loss, as well as in TLE patients with focal lesions but no histopathological alterations of the hippocampus. In contrast, mGluR5 immunoreactivity and mRNA expression were not significantly altered in the DG-ML. Our data demonstrate a striking regional induction of mGluR1alpha in the hippocampal dentate gyrus of experimental animals with limbic seizures as well as in human patients with chronic, intractable TLE. This increase corresponds to functional alterations of class I mGluRs observed in seizure models and may significantly contribute to hippocampal hyperexcitability in focal human epilepsies.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Blümcke I,Becker AJ,Klein C,Scheiwe C,Lie AA,Beck H,Waha A,Friedl MG,Kuhn R,Emson P,Elger C,Wiestler ODdoi
10.1093/jnen/59.1.1subject
Has Abstractpub_date
2000-01-01 00:00:00pages
1-10issue
1eissn
0022-3069issn
1554-6578journal_volume
59pub_type
杂志文章abstract::Progressive multifocal leukoencephalopathy (PML) occurs most often in immunosuppressed individuals. The lesions of PML result from astrocyte and oligodendrocyte infection by the polyomavirus JC (JCV); JCV has also been shown to infect and destroy cerebellar granule cell neurons (GCNs) in 2 human immunodeficiency virus...
journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/NEN.0b013e3181912570
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198001000-00001
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-199704000-00008
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-197809000-00004
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/00005072-199601000-00004
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198009000-00007
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journal_title:Journal of neuropathology and experimental neurology
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doi:10.1097/NEN.0b013e3181461d3e
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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journal_title:Journal of neuropathology and experimental neurology
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