TUESDAY, Sept. 25 (HealthDay News) -- The protein lost in fragile X syndrome, the most common genetic cause of autism, is part of a complex that, when targeted by a drug that boosts a natural marijuana-like chemical in the brain, corrects some of the behavioral abnormalities in mice, according to a study published online Sept. 25 in Nature Communications.
Noting that the fragile X mental retardation protein (FMRP) is lost in patients with fragile X syndrome, and that FMRP regulates signal transduction at metabotropic glutamate receptor-5 (mGlu5) in the brain, Kwang-Mook Jung, Ph.D., from the University of California in Irvine, and colleagues examined whether FMRP deletion affected mGlu5-dependent signaling by the retrograde endocannabinoid transmitter, 2-arachidonoyl-sn-glycerol (2-AG), in mice.
The researchers found that mGlu5-dependent long-term depression at excitatory synapses of the ventral striatum and prefrontal cortex was absent in the mice due to disruption of the complex linking mGlu5 to 2-AG formation. Enhancing 2-AG signaling by small molecules restored endocannabinoid-dependent long-term depression and corrected behavioral abnormalities.
"In conclusion, our results indicate that FMRP expression is necessary for the correct assembling of the endocannabinoid signalosome at glutamatergic synapses of the frontal cortex and ventral striatum core, and identify this macromolecular complex as a previously unknown substrate for fragile X syndrome, which might be targeted by therapy," Jung and colleagues write.
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