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

Full Abstract

PURPOSE: 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. METHODS: The development of alpha 1b-AR knockout (KO) mice led us to measure seizure susceptibility and neurodegeneration following systemic excitotoxins in these mice. RESULTS: 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. CONCLUSIONS: 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 neurotoxicity induced by seizures/chemoconvulsants. These data, although confirming a pivotal role of alpha 1b-AR in modulating seizure threshold and neuronal death, offer a novel target, which may be used to develop novel anticonvulsants and neuroprotective agents.

Author information

Author/s: Pizzanelli, Chiara (C); Lazzeri, Gloria (G); Fulceri, Federica (F); Giorgi, Filippo S (FS); Pasquali, Livia (L); Cifelli, Giuseppe (G); Murri, Luigi (L); Fornai, Francesco (F);

Affiliation: Unit of Neurophysiopathology, Hospital F. Lotti, Pontedera, Pisa, Italy.

Journal and publication information

Publication Type: Comparative Study; Journal Article

Journal: Epilepsia (Epilepsia), published in United States. (Language: eng)

Reference: 2009-Jan; vol 50 Suppl 1 (issue ) : pp 59-64

Dates: Created 2009/01/07; Completed 2009/01/23;

PMID: 19125850, status: MEDLINE (last retrieved date: 2/18/2009)

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