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Alpha‐1A Adrenergic Receptor Overexpression Protects Hippocampal Interneurons
Author(s) -
Knudson Chris Alan,
Carr Patrick A.,
Perez Dianne M.,
Doze Van A.
Publication year - 2007
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.21.6.a1209-a
Subject(s) - hippocampal formation , hippocampus , interneuron , neuroscience , receptor , genetically modified mouse , transgene , biology , microbiology and biotechnology , inhibitory postsynaptic potential , gene , biochemistry
A variety of cytochemically distinct cellular profiles have been shown within the hippocampus, however the synaptic elements whereby the abundant adrenergic input mediates its action remain obscure. Additionally, the lack of highly specific adrenergic receptor (AR) antibodies has reduced the confidence of specific localization of the receptor proteins. To address this issue, a novel model system was utilized in which transgenic mice over‐express the α1A or α1B‐AR fused with EGFP. Sagittal sections of whole brain were double labeled with markers of specific subpopulations of hippocampal neurons and ARs labeled with an anti‐EGFP antibody. Mice which overexpress α1B‐ARs were found to have an age‐dependent decrease in the number of hippocampal interneurons. In contrast, mice overexpressing α1A‐ARs had significantly more hippocampal interneurons. Interestingly, mice overexpressing α1B‐ARs show an increase in seizure development. Alternatively, α1A‐AR overexpression appears to control seizure development through regulation of interneuron function. These results provide anatomical evidence that α1A or α1B‐AR subunits have a diverse distribution among hippocampal neurons with distinct functional identities, which may serve as potential therapeutic targets. This study was funded in part by NIH RO1HL61438 (DMP), NSF CAREER Award 0347259 (VAD), and NIH 5P20RR017699 from the COBRE program (PAC, VAD).