Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease.
Ontology highlight
ABSTRACT: Although postsynaptic glycine receptors (GlyRs) as ?? heteromers attract considerable research attention, little is known about the role of presynaptic GlyRs, likely ? 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 ?1 GlyRs that are responsible for a hereditary startle-hyperekplexia disease. The GlyRs expressed as ?1 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 ?1 GlyRs emerge as a potential therapeutic target for dominant hyperekplexia disease and other diseases with GlyR deficiency.
SUBMITTER: Xiong W
PROVIDER: S-EPMC4019963 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
ACCESS DATA