Fragile X Syndrome (FXS) is a neurodevelopmental disorder resulting from the lack of the protein FMRP due to the transcriptional silencing of the FMR1 gene. FXS is the leading single gene cause of autism, affecting approximately 1 in 4000 males and 1 in 8000 females. Individuals present with intellectual disability, autism, sensory hypersensitivities and epilepsy amongst other comorbidities.

FMRP is ubiquitously expressed throughout the brain and the contribution of neuronal defects to FXS has been widely studied in rodent models of the disorder, with neuronal excitability and network function in the somatosensory cortex thought to contribute to altered sensory processing in FXS. Altered myelination has been reported in FXS individuals as well as in rodent models of the condition. However, the contribution of oligodendrocyte lineage cells and myelination to sensory abnormalities in FXS is not known.

In the current project, I have assessed oligodendrocyte lineage cell numbers and myelination in the somatosensory cortex of Fmr1 KO mice using immunohistochemistry in perfusion fixed brain sections. I have found a reduced number of mature oligodendrocytes (p=0.006, Two-tailed T-test) and an increase in oligodendrocyte progenitor cells (p<0.001, Two-tailed T-test) in Fmr1 KO mice (n=8 mice) relative to WT (n=11 mice), possibly suggesting a developmental delay. This reduction in mature oligodendrocytes was accompanied by a 40% reduction in myelination in the upper layers of the cortex in Fmr1 KO mice (p<0.001, Two-tailed T-test), suggesting altered developmental myelination may contribute to altered somatosensory cortex function in FXS. I am currently testing whether pro-myelinating drugs can rescue the myelination phenotype and recover neuronal function.

All experiments were performed in accordance with institutional (University of Edinburgh, UK) and UK Home Office guidelines (ASPA, PPL: PP5764018).