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Klinische Neurophysiologie 2002; 33(3): 120-127
DOI: 10.1055/s-2002-34832
Originalia
© Georg Thieme Verlag Stuttgart · New York

Transmitterrezeptorenverteilung im chronisch epileptogenen Hirngewebe des Menschen

Transmitter Receptor Distribution in Chronic Epileptogenic Human Brain TissueH. G.  Wieser1 , F.  Loup2 , J.-M.  Fritschy2
  • 1Abteilung für Epileptologie und Elektroenzephalographie, Neurologische Klinik und Poliklinik, Universitätsspital Zürich
  • 2Institut für Pharmakologie und Toxikologie, Universität Zürich
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Publication History

Publication Date:
17 October 2002 (online)

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Zusammenfassung

Die mesiale Temporallappenepilepsie (MTLE), die häufigste Epilepsieform in epilepsiechirurgischen Serien, ist vergesellschaftet mit Hippokampussklerose (HS). HS ist charakterisiert durch Nervenzellverlust und durch reaktive Gliose in allen Ammonshornfeldern und der Fascia dentata. Am stärksten betroffen ist das Cornu ammonis (CA) Feld CA1 und das Prosubikulum. Gewöhnlich ist die vordere Hippokampusformation schwerer betroffen als der posteriore Anteil. In der synaptisch reorganisierten Fascia dentata und im Hippokampus kommt es zu einer pathologischen Umverteilung vorwiegend der Moosfasern („mossy fiber sprouting”), welche jetzt Dendriten - die durch den Nervenzellverlust denerviert wurden - hyperinnervieren. Hinsichtlich exzitatorischen Transmitterveränderungen referieren wir einige neuere Befunde im Zusammenhang mit kortikalen Dysplasien. Wir selbst untersuchten das inhibitorische GABA-System, einerseits mit In-vivo-1H-Magnetresonanzspektroskopie, andererseits im epilepsiechirurgisch resezierten Hippokampus. Dabei interessierte uns vor allem, ob und wie GABAA-Rezeptor-Subtypen im epileptogenen Hippokampus des Menschen verändert sind. Loup et al. [1] konnten zeigen, dass 1. im normalen menschlichen Hippokampus ein unterschiedliches neuronspezifisches Expressionsmuster von GABAA-Rezeptor-Untereinheiten vorhanden ist, und zwar sowohl auf regionaler Ebene als auch auf Zell-Ebene. 2. In MTLE-Patienten gab es in Gebieten mit deutlichem Nervenzellverlust generell ein vermindertes Expressionsmuster von GABAA-Rezeptor-Untereinheiten. Überlebende Nervenzellen wiesen hingegen spezifische Veränderungen im Expressionsmuster der drei wichtigsten GABAA-Rezeptor-Untereinheiten auf. Die augenfälligsten Veränderungen betrafen a) eine verstärkte Anfärbung für spezifische GABAA-Rezeptor-Untereinheiten in den Zellkörpern und apikalen Dendriten der Körnerzellen bei gleichzeitig verminderter Anfärbung der basalen Dendriten, b) unterschiedliche Reorganisation der α1-, α2-, und α3-Untereinheiten in CA2 und in Zellen des Hilus, c) partieller und schichtenspezifischer Verlust von α1-untereinheitpositiven Interneuronen im Hippokampus proper, und d) Veränderungen der Morphologie in vielen überlebenden Interneuronen, welche immunpositiv für die α1-Unterheinheit sind.

Abstract

Mesial temporal lobe epilepsy (MTLE), the most frequent type of epilepsy in surgical series, is associated with hippocampal sclerosis (HS). HS is characterized by neuronal loss and reactive gliosis in all fields of Cornu Ammonis (CA) and the fascia dentata, but CA1 and the prosubiculum show the most severe sclerotic changes, and usually the anterior hippocampus is more severely affected than the posterior part. In the synaptically reorganized fascia dentata a pathological rearrangement, in particular of the mossy fibers („mossy fiber sprouting”), is observed, which leads to hyperinnnervation of previously denervated dendrites due to neuronal loss. With reference to changes of excitatory neurotransmitters we report some recent findings in the context of cortical dysplasia. Our own research concentrated on the inhibitory GABA system with In-vivo 1H-magnetic resonance spectroscopy, and on immunohistochemical studies in resected epileptogenic hippocampi. In particular, we examined whether and how GABAA receptor subtypes are altered in human epileptogenic hippocampus. Loup et al. [1] showed that 1. in the normal human hippocampus a differential and neuron-specific expression pattern of GABAA receptor subunits is evident, both at the regional and the cellular level. 2. In MTLE patients with HS, staining is decreased in areas of prominent cell loss, whereas surviving neurons exhibit selective alterations in the expression of the three major GABAA receptor subtypes. The most striking changes are a) increased staining for distinct GABAA receptor subunits on the somata and apical dendrites of granule cells with reduced labelling on the basal dendrites, b) differential reorganization of the α1-, α2-, and α3-subunits in the CA2 area and in hilar cells, c) partial and layer-specific loss of α1-subunit-positive interneurons in the hippocampus proper, and d) altered dendritic morphology in many of the surviving interneurons immunopositive for the α1-subunit.

Key words

Mesial temporal lobe epilepsy - Hippocampal sclerosis - Transmitters, GABAA receptor subtype alterations in human epileptogenic hippocampus

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Prof. Dr. med. Heinz Gregor Wieser

Abteilung für Epileptologie und Elektroenzephalographie · Neurologische Klinik · Universitätsspital

8091 Zürich · Schweiz

Email: hgwepi@neurol.unizh.ch

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