Strain differences in proliferation of progenitor cells in the dentate gyrus of the adult rat and the response to fluoxetine are dependent on corticosterone

Abstract

This paper investigates the role of differences in adrenal cortical function on the proliferation rate of progenitor cells in the dentate gyrus of the hippocampus in adult Sprague-Dawley (SD) and Lister-Hooded (LH) male rats. SD rats had around 60% more cells labeled with Ki67 (an index of mitosis) than LH rats under basal conditions. Bilateral adrenalectomy (ADX) increased levels in both strains, but by unequal amounts, such that post-ADX numbers of Ki67-labeled cells were similar in both strains. Daily injections of 5 mg/kg corticosterone for 7 days reduced levels to similar values in ADX rats of both strains. The activity of progenitor cells in either strain did not respond to daily i.p. injections of fluoxetine (10 mg/kg) for 14 days, but an equivalent dose administered by osmotic minipump stimulated proliferation in both by a similar proportional amount, such that strain differences persisted. S.c. implantation of a corticosterone pellet (75 mg), which flattens the diurnal rhythm in corticosterone, prevented fluoxetine delivered by minipump from activating progenitor cell mitosis in SD rats, as it had in the LH strain in a previous study. These results show that much, if not all, of the marked strain differences between SD and LH rats in progenitor cell activity, and hence rates of neurogenesis in the dentate gyrus may be ascribed to corresponding differences in adrenal cortical activity.

Fig. 1

Photomicrographs of coronal sections (20 μm) through the dentate gyrus of (a) LH (b) SD strains of rats. Ki67-labeled cells are indicated by the arrows. Cresyl Violet background stain. Scale bar=500 μm.

Fig. 2

Number (mean per section±S.E.M.) of Ki67-labeled cells after either (a) i.p. saline (white bars) or fluoxetine (black bars) (c) saline- or fluoxetine-filled minipumps. (b, d) Plasma corticosterone levels in the same animals within 4 min of lethal injection of pentobarbital (at CT12). Significance levels (two-way ANOVA) given in text.

Fig. 3

The effect of ADX and corticosterone replacement (5 mg/kg/day for 7 days) on cell proliferation (Ki67 counts) in the adult dentate gyrus of LH and SD strains. Significance levels (two-way ANOVA) given in text.

Fig. 4

Effect of an s.c. pellet of corticosterone (75 mg) in intact SD rats on cell proliferation (Ki67 counts) in the dentate gyrus in control and fluoxetine-treated rats (osmotic minipumps). Results of two-way ANOVA given in text: significance levels of Bonferroni tests shown on fig: ** P<0.01.