Sex Is a Major Determinant of Neuronal Dysfunction in Neurofibromatosis Type 1

摘要: Objective: Children with neurofibromatosis-1 (NF1) are at risk for developing numerous nervous system abnormalities, including cognitive problems and brain tumors (optic pathway glioma). Currently, there few prognostic factors that predict clinical manifestations or outcomes in patients, even families an identical NF1 gene mutation. In this study, we leveraged Nf1 genetically engineered mice (GEM) to define the potential role of sex as a clinically relevant modifier NF1-associated neuronal dysfunction. Methods: Deidentified data were analyzed determine impact on optic glioma–associated visual decline children NF1. addition, GEM employed experimental platforms investigate sexually dimorphic differences learning/memory, acuity, retinal ganglion cell (RGC) death, protein (neurofibromin)-regulated signaling function (Ras activity, cyclic adenosine monophosphate [cAMP], dopamine levels). Results: Female patients glioma twice likely undergo magnetic resonance imaging symptoms 33 more require treatment than their male counterparts. As such, only female exhibited decrement shorter RGC axons, attenuated cAMP levels. contrast, showed spatial learning/memory deficits, increased Ras reduced Interpretation: Collectively, these observations establish major factor underlying dysfunction NF1, suggest should be considered when interpreting future preclinical study results.