| First Author | Xiong W | Year | 2014 |
| Journal | Nat Neurosci | Volume | 17 |
| Issue | 2 | Pages | 232-9 |
| PubMed ID | 24390226 | Mgi Jnum | J:207996 |
| Mgi Id | MGI:5560410 | Doi | 10.1038/nn.3615 |
| Citation | Xiong W, et al. (2014) Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nat Neurosci 17(2):232-9 |
| abstractText | Although postsynaptic glycine receptors (GlyRs) as alphabeta heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely alpha 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 alpha1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease. The GlyRs expressed as alpha1 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 alpha1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency. |
