Genetic essential tremor in &upsih-aminobutyric acid<subscript>A</subscript> receptor α1 subunit knockout mice.
In: Journal of Clinical Investigation, Jg. 115 (2005-03-01), Heft 3, S. 774-779
academicJournal
Zugriff:
Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that γ-aminobutyric acidA (GABAA) receptor a1-/- mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D- aspartate receptor antagonist MK-801; the adenosine Al receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABAA receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebeilar Purkinje cells in GABAA receptor a1-/- mice exhibited a profound loss of all respons- es to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor. [ABSTRACT FROM AUTHOR]
Titel: |
Genetic essential tremor in &upsih-aminobutyric acid<subscript>A</subscript> receptor α1 subunit knockout mice.
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Autor/in / Beteiligte Person: | Kralic, Jason E. ; Criswell, Hugh E. ; Osterman, Jessica L. ; O'buckley, Todd K. ; Wilkie, Mary E. ; Matthews, Douglas B. ; Hamre, Kristin ; Breese, George R. ; Homanics, Gregg E. ; Leslie Morrow, A. |
Zeitschrift: | Journal of Clinical Investigation, Jg. 115 (2005-03-01), Heft 3, S. 774-779 |
Veröffentlichung: | 2005 |
Medientyp: | academicJournal |
ISSN: | 0021-9738 (print) |
DOI: | 10.1172/JCI200523625 |
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