Astrocytic Influences in the Auditory Brainstem in Fragile X Syndrome

Abstract

Fragile X Syndrome is one of the leading genetic causes of autism spectrum disorder. Fragile X Syndrome is associated with auditory hypersensitivity and childhood audiogenic frontal-temporal lobe seizures, which may be the result of abnormalities in the auditory nuclei found in the brainstem. The purpose of this research is to expand on preliminary findings that dysfunction in the auditory brainstem contributes to sound sensitivity and subsequently to frontal-temporal lobe seizures. To test the role of the LSO, VCN, and MNTB we examined the astrocyte function in these areas by extracting the auditory brainstem from Fmr1 KO mice and wild type mice. We then co-cultured these astrocytes with neurons from either mouse genotype to determine differences in the neuronal size, morphology, and synaptogenic factors. Our research examined the levels of SPARC, hevin, and thrombospondin-1, which are synaptic proteins found in the synapses in the auditory brainstem. Our results showed that Fmr1 KO astrocytes altered the size of WT neurons to a size comparable to a standard Fmr1 KO neuron, and Fmr1 KO astrocytes secreted significantly less SPARC than WT astrocytes. Overall, abnormal astrocyte function among Fmr1 KO mice was found to cause morphological changes in auditory brainstem neurons and differences in the amount of the SPARC found in the auditory brainstem between wild type and Fmr1 KO mice.