Introduction: The purpose of this study was to determine if pharmacological treatment
could increase progenitor cell proliferation in the Sub-ventricular Zone of aged rats. Previous work
had shown that increasing progenitor cell proliferation in this region correlated well (R2=0.78; p=
0.0007) with functional recovery in a damaged corpus callosum (white matter tract), suggesting that
progenitor cell proliferation results in oligodendrocytes in this region.
Methods: 10 month old male and female Sprague Dawley rats were fed the drugs for 30 days in cookie
dough, then immunocytochemistry was performed on coronal brain sections, using Ki67 labeling to
determine progenitor cell proliferation.
Results: Female rats showed low endogenous (control) progenitor cell proliferation, significantly different
from male rats (P<0.0001), at this age. Ascorbic Acid (20 mg/kg, daily for 30 days) increased
progenitor cell proliferation overall, but maintained the innate gender difference in stem cell proliferation
(P=0.001). Prozac (5 mg/kg, daily for 30 days) increased progenitor cell proliferation for females
but decreased stem cell proliferation for males, again showing a gender difference (P<0.0001).
Simvastatin (1 mg/kg for 30 days) also increased progenitor cell proliferation in females and decreased
progenitor cell proliferation in males, leading to a significant gender difference.
Discussion: The three drug combinations (fluoxetine, simvastatin, and ascorbic acid, patent #
9,254,281) led to ~ 4 fold increase in progenitor cell proliferation in females, while male progenitor
cell proliferation was highest with 50 mg/kg ascorbic acid. However, the ascorbic acid increase in proliferation
appears to be only on the sides of the ventricles, which is not the region that normally gives
rise to oligodendrocytes.
Conclusion: There are innate gender differences in progenitor cell proliferation at the Sub-Ventricular
Zone at middle age in rats, possibly due to the loss of estrogen in females. We also see notable gender
differences in progenitor cell proliferation in the Sub ventricular Zone in response to common drugs,
such as fluoxetine, simvastatin and Vitamin C (ascorbic acid).