Theses and Dissertations

Date of Award


Document Type


Degree Name

Master of Science (MS)


Biochemistry and Molecular Biology

First Advisor

Alejandro Lopez-Juarez

Second Advisor

Megan Keniry

Third Advisor

Julie Mustard


Neurofibromatosis Type 1 (NF1) is an autosomal dominant disease caused by mutations in the NF1 gene, on chromosome 17. NF1 patients suffer from a number of neurological issues including learning deficits and increased risk of age-related dementia. Additionally, NF1 patients present with multiple white matter and myelin abnormalities. Whether and how myelin abnormalities impact learning in NF1 is not known; therefore, we aimed to gain insights on potential links between Nf1 mutation and learning issues Unpublished data indicate that NF1 female-but not male- mice with Nf1+/- germline mutation show defects in a myelin-regulated learning/memory test (the complex wheel; CW) at 3 months of age, and that oligodendrocyte (OL; the CNS myelinating cells) progenitors (OPCs) show progressive abnormalities in their cell density thereafter; regional, gender-driven, or learning phenotypes in aging mice remain unknown. Here, we used adult/aging NF1 mice (12-month-old; 12MO) to define OPC-OL numbers and their proliferation rate at basal levels and after the CW test learning challenge. We found modestly increased OPCs in regions of the corpus callosum (CC) of unchallenged Nf1 mutant male and female mice, yet with decreased proliferation. This suggests that abnormally accumulated OPCs seen in younger NF1 mice persists in specific brain regions at 12 MO despite low proliferation. Interestingly, 12 MO Nf1+/- females subjected to the CW challenge show decreased learning as compared with control mice. Low activity and learning were observed in both control and Nf1+/- aging males, likely precluding development of phenotypes. Remarkably, while OPCs and/or OL numbers showed regional increases in control females after the learning challenge, OPC numbers decrease or remain unchanged and OLs numbers did not change in NF1 mice, suggesting abnormal lineage progression. Moreover, regionally reduced proliferation was also found in Nf1+/- females after the learning test. Overall, our study suggests that myelin biology impacts learning in aging NF1 female mice, and this could be a mechanism for the increased risk of age-related dementia in female patients.


Copyright 2023 Saul Lopez. All Right Reserved.

Available for download on Monday, December 01, 2025