Effects of long-term hormone treatment on cognitive behavior and the structure of the medial prefrontal cortex during aging in female rats

Although previous research has indicated that hormone replacement therapy benefits memory in menopausal women, several newer studies have shown no effect or detrimental effects. These inconsistencies emphasize the need to evaluate the role of hormones in protecting against agerelated cognitive decline in an animal model. Furthermore, research has found that ovarian hormones alter brain structure and function. However, many studies evaluating the effects of estrogen and progesterone on brain structure have used young adult animals and have not administered medroxyprogesterone acetate (MPA), the most commonly prescribed progestin. The aging brain may respond differently to the presence of these hormones. Therefore, the effects of long-term hormone treatment during aging on cognition and neuroanatomy were investigated. Female Long Evans hooded rats were ovariectomized at middle age (12-14 months) and placed in one of 5 groups: no replacement, chronic estrogen only, chronic estrogen and progesterone, chronic estrogen and MPA, and cyclic estrogen. Hormone treatment continued until sacrifice. Estrogen was administered in the drinking water. Progesterone and MPA were administered with subcutaneous pellets. Following five months of hormone replacement, animals were tested on a delayed alternation task in the T-maze. Two weeks after completing the T-maze animals were tested in the Morris water maze. At approximately 20 months of age, animals were sacrificed and their brains were sectioned and using immunohistochemistry, stained for tyrosine hydroxylase and synaptophysin. Adjacent sections were Nissl stained to calculate volume and quantify neuron number. The medial prefrontal cortex was examined because it is involved in several cognitive tasks and is known to be sensitive to both aging and ovarian hormones. Using unbiased stereology and light microscopy, neuron number and synaptophysin labeled boutons iii were quantified. Images were acquired of the tyrosine hydroxylase sections using Axiovision (Zeiss) on a fluorescent microscope and fiber densities were quantified. Behavioral results found that animals receiving estrogen in combination with MPA acquired the t-maze faster than no replacement animals, but there were no differences in performance on the delayed portion of the task. However, on the Morris water maze, animals receiving this hormone treatment were impaired as compared to other hormone treated groups. Estrogen in combination with MPA resulted in greater synaptophysin levels in the medial prefrontal cortex. Analysis of tyrosine hydroxylase fibers found that animals receiving estrogen in combination with MPA consistently had significantly higher tyrosine hydroxylase pixel densities than no replacement animals. Hormone treatment did not significantly alter neuron number in the medial prefrontal cortex. These results indicate that the effects of long-term hormone treatment are task specific and longterm hormone treatments alter dopaminergic functioning and synapse number in the medial prefrontal cortex, providing a possible mechanism by which long-term hormone treatments can influence cognition. Importantly, these beneficial neural outcomes were observed in groups receiving estrogen in combination with the controversial progestin, MPA.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Psychology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Chisholm, Nioka

Contributors dc:contributor

• Juraska, Janice M.
• Schantz, Susan L.
• Roy, Edward J.
• Galvez, Roberto
• Mahoney, Megan M.

• Cognition
• Medroxyprogesterone Acetate
• Aging
• Estrogen
• Prefrontal Cortex
• hormone Treatment

Statement dc:rights

• Copyright 2012 Nioka Chisholm

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/30933

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/30933