Lack of alpha 1b-adrenergic receptor protects against epileptic seizures

Epilepsia
Chiara PizzanelliFrancesco Fornai

Abstract

The role of alpha 1b-adrenergic receptor (alpha 1b-AR) in relation with neuronal degeneration, drug addiction, and seizure susceptibility has recently emerged. In particular, mice that overexpress alpha 1b-AR undergo spontaneous epileptic seizures and progressive neuronal loss in a variety of brain areas. Therefore, one should expect that the blockade of alpha 1b-AR leads to anticonvulsant and neuroprotective effects. However, the lack of alpha 1b-AR antagonists does not allow testing of this hypothesis. The development of alpha 1b-AR knockout (KO) mice led us to measure seizure susceptibility and neurodegeneration following systemic excitotoxins in these mice. We found that alpha 1b-AR KO mice are markedly resistant to kainate- and pilocarpine-induced seizures. Moreover, when marked seizure duration and severity are obtained by doubling the dose of chemoconvulsants in alpha 1b-AR KO, neuronal degeneration never occurs. These data indicate that alpha 1b-AR per se plays a fundamental role in the mechanisms responsible for seizure onset, severity, and duration, whereas the brain damage observed in alpha 1b-AR-overexpressing mice is likely to be a secondary phenomenon. In fact, the absence of alpha 1b-AR confers resistance to neur...Continue Reading

References

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Citations

Jun 3, 2009·Molecular Pharmacology·Manveen K GuptaDianne M Perez
May 4, 2011·The European Journal of Neuroscience·Francesco FornaiAntonio Paparelli
Jul 6, 2010·Arquivos de neuro-psiquiatria·Adriana da Rocha ToméRivelilson Mendes de Freitas
Feb 23, 2011·Journal of Receptor and Signal Transduction Research·Dianne M Perez, Van A Doze
Mar 11, 2010·Current Opinion in Neurology

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