Olga Neyman

Program: Neurosciences

Current advisor: Tamara Hershey, PhD

Undergraduate university: Washington University

Research summary
Wolfram syndrome is a rare, autosomal recessive disease traditionally characterized by juvenile onset insulin dependent diabetes, optic atrophy, deafness, and neurodegeneration often beginning in childhood and adolescence. The disease is caused by mutations in WFS1, which encodes for the protein wolframin and is associated with endoplasmic (ER) stress-mediated apoptosis. ER stress-related dysfunction may inhibit production of myelin during neurodevelopment in Wolfram syndrome, as active and developing oligodendrocytes are more vulnerable to ER stress than mature ones. It is known that white matter tracts are compromised in the disease, but many questions related to the vulnerability of myelin and its impact on the disease remain. I characterized the developmental trajectory of myelin in both white and gray matter and examined how differences in myelin in Wolfram syndrome correlate to disease presentation. I also examined a novel mouse model of the disease to see how well any myelin pathology in the model mirrors what is seen in humans.
The human studies determined that a decreased rate of myelination in Wolfram syndrome as compared to controls throughout most of the brain, with a divergence in myelin integrity in early adulthood. However, tracts associated with visual processing were clearly hypomyelinated in early childhood followed by a normal rate of increased myelination over age. On the other hand, gray matter myelin was found to be largely conserved in the disease. Symptom severity was correlated to whole brain white matter myelin integrity markers in the brain, but lacked specificity, i.e. visual acuity was not correlated with markers in the optic radiations. The mouse model analysis found some differences in myelin integrity in regions such as the optic tracts, but was overall found to not be a sufficiently good model of the neuronal phenotype on Wolfram syndrome.
Together, these studies confirm the strong involvement of white matter integrity in the pathology of the disease. They suggest a regionally specific pattern of vulnerability in the timing and rate of myelin development, and a broad relationship between the level of myelin integrity and severity of disease. These findings are crucial for the betterment of our understanding of this severe disease and will facilitate the identification of therapeutic targets and biomarkers to evaluate the efficacy of potential treatments.

Graduate publications
Samara A, Murphy T, Strain J, Rutlin J, Sun P, Neyman O, Sreevalsan N, Shimony JS, Ances BM, Song SK, Hershey T. 2020 Neuroinflammation and White Matter Alterations in Obesity Assessed by Diffusion Basis Spectrum Imaging. Front Hum Neurosci, 13():464.

Samara A, Rahn R, Neyman O, Park KY, Samara A, Marshall B, Dougherty J, Hershey T. 2019 Developmental hypomyelination in Wolfram syndrome: new insights from neuroimaging and gene expression analyses. Orphanet J Rare Dis, 14(1):279.

Lugar HM, Koller JM, Rutlin J, Eisenstein SA, Neyman O, Narayanan A, Chen L, Shimony JS, Hershey T. 2019 Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry. Sci Rep, 9(1):6010.

Neyman, O., Snyder, A., Arbelaez, A.M., Mitra, A. Hershey, T., Raichle, M.. (2017) The Effect of Acute Hyperglycemia on Resting State Functional Connectivity Networks. Society for Neuroscience, Wasington, D.C., Abstract.

Rahn R, Park K, Neyman O, Dougherty J, Hershey T. (2016) Wolfram Syndrome and the Brain: A Bioinformatics Analysis of WFS1 Expression. Pediatric Diabetes Research Consortium, St. Louis, MO, Abstract.

Neyman O, Snyder A, Shimony J, Koller J, Hershey T. (2016) The Impact of Diabetes and Wolfram Syndrome on Functional Connectivity. Diabetes Day Symposium, St. Louis, MO, Abstract.

Neyman O, Snyder A, Shimony J, Koller J, Hershey T. (2016) The Impact of Diabetes and Wolfram Syndrome on Functional Connectivity. Flux Congress, St. Louis, MO, Abstract.