University Honors

As one of the principal inherited forms of intellectual disability and parallels with autism spectrumdisorder, Fragile X syndrome (FXS) can cause severe behavioral alterations due to specific geneticmutations. Fragile X syndrome is caused by a mutation in the fragile X messengerribonucleoprotein 1 (Fmr1) gene. The silencing of this gene causes a loss of the fragile Xmessenger ribonucleoprotein 1 protein (FMRP), which binds to mRNAs to dictate neuralprocessing from synaptogenesis to regulation of cell-to-cell communication. Symptoms of FragileX syndrome include difficulties in language processing and cognition, delayed development ofcommunication, learning disabilities, and repetitive behaviors. Since there is no definitive cure forFragile X syndrome, there continue to be experiments conducted that aim to test various drugstargeting abnormal phenotypes caused by the disorder, one of which includes roflumilast.Roflumilast is a phosphodiesterase four inhibitor that has been shown to improve cyclic AMPpathway (cAMP) signaling in neurological disorders. cAMP signaling is crucial for organisms asit facilitates communication for intracellular processes regarding proliferation, differentiation, andapoptosis. In Fragile X syndrome, cAMP signaling exhibits dysregulation, which can impact thebehavioral and cognitive functioning of those affected. Due to this, we will study roflumilast todetermine whether it can normalize abnormal behavioral phenotypes in a mouse model of FragileX syndrome.