Audiogenic seizures and effects of mGluR5 agonist MPEP in the Fragile X mouse - 2006

mGluR receptors have been implicated in the abnormal neuronal responses observed in Fragile X syndrome. To address whether reversing mGluR signaling alterations might ameliorate the effects of Fragile X, we have tested a drug,MPEP, which specifically blocks one type of group 1 mGluR receptor (mGluR5). Using MPEP, we have been able to reverse the susceptibility that Fragile X mice have to audiogenic seizures, which are triggered by very loud sound.

We have also shown that the degree of rescue is equivalent to that found by placing a copy of the human FMR1 gene into the genome of Fragile X mice, suggesting that MPEP can compensate for lack of FMRP in protecting against audiogenic seizures.We are also testing the effects of mGluR5 antagonists in other learning and behavioral assays. Finally, we are producing new mouse models of Fragile X which might give more robust learning deficits comparable to those observed in humans. If that is the case, we will use such animals to further assess the effectiveness of mGluR antagonists and other compounds on Fragile X cognition.