Back to Search
Start Over
Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease.
- Source :
-
Nature Neuroscience . Feb2014, Vol. 17 Issue 2, p232-239. 8p. 6 Graphs. - Publication Year :
- 2014
-
Abstract
- Although postsynaptic glycine receptors (GlyRs) as αβ heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely α homomers, in diseases. Here, we demonstrate that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, can rescue GlyR functional deficiency and exaggerated acoustic and tactile startle responses in mice bearing point mutations in α1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease. The GlyRs expressed as α1 homomers either in HEK-293 cells or at presynaptic terminals of the calyceal synapses in the auditory brainstem are more vulnerable than heteromers to hyperekplexia mutation-induced impairment. Homomeric mutants are more sensitive to DH-CBD than are heteromers, suggesting presynaptic GlyRs as a primary target. Consistent with this idea, DH-CBD selectively rescues impaired presynaptic GlyR activity and diminished glycine release in the brainstem and spinal cord of hyperekplexic mutant mice. Thus, presynaptic α1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10976256
- Volume :
- 17
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Nature Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 94081235
- Full Text :
- https://doi.org/10.1038/nn.3615