The Effects of Long-Term Treatment with Estradiol and Medroxyprogesterone Acetate on Tyrosine Hydroxylase Fibers and Neuron Number in the Medial Prefrontal Cortex of Aged Female Rats

Abstract

Menopausal women often initiate hormone treatment to alleviate the symptoms of menopause. Research suggests that these treatments also affect cognition, and studies in young animals indicate that hormone treatment can alter several neuroanatomical measures. However, very little is known about the effects of long-term hormone treatment on the aging female brain. This study investigated the effects of hormone treatment on neuron number and tyrosine hydroxylase (TH) in the rat medial prefrontal cortex (mPFC). Female Long Evans rats were ovariectomized at middle age (12-13 months) and placed in one of four groups: no replacement (NR) (n = 12), 17β-estradiol (E(2)) (n = 12), E(2) and progesterone (n = 7), or E(2) and medroxyprogesterone acetate (MPA) (n = 10). Animals were euthanized at 20 months, and the brains were Nissl stained; a subset was immunostained for TH [NR (n = 5); E(2) (n = 6); E(2) + MPA (n = 4); E(2) + progesterone (n = 6)]. E(2) was administered through the drinking water, and progestagens were administered via pellets inserted at the nape of the neck. Neuron number and TH fiber density were quantified in the mPFC. Hormone treatment did not alter neuron number. Treatment with E(2) and MPA resulted in greater TH densities than NR in layer 1 (P < 0.05). In layers 2/3, animals receiving E(2) had greater TH densities than NR animals (P < 0.01). These results indicate that long-term hormone treatments alter dopaminergic fibers and potentially the functioning of the aging mPFC.