Open Access Dissertation
Date of Award
Anatomy and Cell Biology
Robert P. Skoff
Multiple sclerosis is a sexually dimorphic (SD) disease that causes oligodendrocyte death but SD of glial cells is poorly studied. Here, we analyze SD of neural progenitors in 6-8wk and 6-8mo normal C57BL/6, SJL/J and BALB/c mice in the subventricular zone (SVZ), dorsolateral horn (DLC), corpus callosum (CC), and parenchyma. With a short 2 h BrdU pulse, no gender and strain differences are present at 6-8wk. At 6-8mo, the number of BrdU+ cells decreases 2-fold in both sexes, strains and regions indicating a common aging mechanism regulates BrdU incorporation. Strikingly, 2X more BrdU+ cells are found in all brain regions in 6-8mo C57BL/6 females vs males, no gender differences in 6-8mo SJL/J, and fewer BrdU+ cells in females vs males in BALB/c's. The number of BrdU+ cells modestly fluctuates throughout the estrous cycle in C57BL/6 and SJL's. Castration causes a dramatic increase in BrdU+ cells in SVZ and DLC. These findings indicate testosterone is a major regulator of adult neural proliferation. At 6-8mo, the ratio of PDGFRa+ cells in the CC to BrdU+ cells in the DLC of both strains, sexes, estrous cycle and castrated mice was essentially the same, suggesting BrdU+ cells in the DLC differentiate into CC oligodendrocytes. The ratio of TUNEL+ to BrdU+ cells does not match proliferation, indicating these events are differentially regulated. Differential regulation of these two processes leads to variation in glial numbers between gender and strain. Explanations of neural proliferation based upon data from one sex or strain may be very misleading.
Tatar, Carrie Lynn, "Determinants of cns adult neurogenesis are sex, hormones, mouse strain, age, and brain region" (2012). Wayne State University Dissertations. Paper 521.