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Alpha‐1 adrenergic receptor regulation of seizures and neurodegeneration
Author(s) -
Goldenstein Brianna,
Jurgens Chris,
Knudson Chris,
Lichter Jessica,
Carr Patrick,
Perez Dianne
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.748.12
Subject(s) - neurogenesis , neuroscience , neurodegeneration , epilepsy , hippocampal formation , knockout mouse , agonist , neurotransmitter , neuropharmacology , hippocampus , receptor , medicine , biology , central nervous system , disease
Neurogenesis has potential as a treatment for epilepsy and neurodegeneration. The endogenous neurotransmitter norepinephrine (NE) may be involved in promoting neurogenesis through the activation of α 1 adrenergic receptors (ARs). This project aims to obtain additional evidence for a possible role of α 1 ARs in neurogenesis and seizures using transgenic mice overexpressing α 1A ARs or α 1B ARs or having no functional (knockout) α 1A ARs or α 1B ARs. When treated with the epileptogenic agent flurothyl and compared to controls, mice overexpressing α 1A ARs had more hippocampal interneurons and showed an increase in latency periods preceding seizures while α 1B AR overexpressing mice had significantly fewer interneurons and exhibited an enhanced susceptibility to seizures. Electrophysiological recordings during application of an α 1 AR agonist produced a concentration‐dependent increase in action potential frequency in hippocampal interneurons in normal and α 1B AR knockout mice, but not in α 1A AR‐knockout mice. These findings are potentially very significant because they link α 1A AR‐induced proliferation of interneurons to the antiepileptic actions of NE. Insight into these mechanisms may lead to new treatment strategies for epilepsy and other neurodegenerative diseases. Supported by ND EPSCoR through NSF EPS‐0447679, NSF CAREER 0347259, NIH 5P20RR017699 from the NCRR, and the American Physiological Society.