Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures (Articolo in rivista)

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  • Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures (Articolo in rivista) (literal)
Anno
  • 2007-01-01T00:00:00+01:00 (literal)
Alternative label
  • D. Merlo a,c,1; C. Mollinari a,1; Y. Inaba b; A. Cardinale c; A.M. Rinaldi d; M. D'Antuono d; G. D'Arcangelo d; V. Tancredi d; D. Ragsdale b; M. Avoli b,e 1. Authors equally contributed to the work (2007)
    Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures
    in Neurobiology of disease
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • D. Merlo a,c,1; C. Mollinari a,1; Y. Inaba b; A. Cardinale c; A.M. Rinaldi d; M. D'Antuono d; G. D'Arcangelo d; V. Tancredi d; D. Ragsdale b; M. Avoli b,e 1. Authors equally contributed to the work (literal)
Pagina inizio
  • 631 (literal)
Pagina fine
  • 641 (literal)
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  • 25 (literal)
Rivista
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  • 3 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • a Istituto Superiore di Sanità, Dipartimento di Biologia Cellulare e Neuroscienze, 00161 Rome, Italy b Montreal Neurological Institute and Departments of Neurology and Neurosurgery, and of Physiology, McGill University, Montréal, QC, Canada H3A 2B4 c IRCCS San Raffaele Pisana, 00163 Rome, Italy d Dipartimento di Neuroscienze, Università di Roma \"Tor Vergata\", 00133 Roma, Italy e Dipartimento di Fisiologia Umana e Farmacologia, Università di Roma \"La Sapienza\", 00185 Roma, Italy (literal)
Titolo
  • Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures (literal)
Abstract
  • Neocortical networks play a major role in the genesis of generalized spike-and-wave (SW) discharges associated with absence seizures in humans and in animal models, including genetically predisposed WAG/Rij rats. Here, we tested the hypothesis that alterations in GABAB receptors contribute to neocortical hyperexcitability in these animals. By using Real-Time PCR we found that mRNA levels for most GABAB(1) subunits are diminished in epileptic WAG/Rij neocortex as compared with age-matched non-epileptic controls (NEC), whereas GABAB(2) mRNA is unchanged. Next, we investigated the cellular distribution of GABAB(1) and GABAB(2) subunits by confocal microscopy and discovered that GABAB(1) subunits fail to localize in the distal dendrites of WAG/Rij neocortical pyramidal cells. Intracellular recordings from neocortical cells in an in vitro slice preparation demonstrated reduced paired-pulse depression of pharmacologically isolated excitatory and inhibitory responses in epileptic WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC slices was diminished by a GABAB receptor antagonist to a greater extent than in WAG/Rij rats further suggesting GABAB receptor dysfunction. In conclusion, our data identify changes in GABAB receptor subunit expression and distribution along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex. We propose that these alterations may contribute to neocortical hyperexcitability and thus to SW generation in absence epilepsy. (literal)
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