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

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

Chisholm, Nioka

关键词: Aging;    Estrogen;    Prefrontal Cortex;    Cognition;    Medroxyprogesterone Acetate;    hormone Treatment;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/30933/Chisholm_Nioka.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Although previous research has indicated that hormone replacement therapy benefits memory inmenopausal women, several newer studies have shown no effect or detrimental effects. Theseinconsistencies emphasize the need to evaluate the role of hormones in protecting against agerelatedcognitive decline in an animal model. Furthermore, research has found that ovarianhormones alter brain structure and function. However, many studies evaluating the effects ofestrogen and progesterone on brain structure have used young adult animals and have notadministered medroxyprogesterone acetate (MPA), the most commonly prescribed progestin.The aging brain may respond differently to the presence of these hormones. Therefore, theeffects of long-term hormone treatment during aging on cognition and neuroanatomy wereinvestigated. 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 andprogesterone, chronic estrogen and MPA, and cyclic estrogen. Hormone treatment continueduntil sacrifice. Estrogen was administered in the drinking water. Progesterone and MPA wereadministered with subcutaneous pellets. Following five months of hormone replacement, animalswere tested on a delayed alternation task in the T-maze. Two weeks after completing the T-mazeanimals were tested in the Morris water maze. At approximately 20 months of age, animals weresacrificed and their brains were sectioned and using immunohistochemistry, stained for tyrosinehydroxylase and synaptophysin. Adjacent sections were Nissl stained to calculate volume andquantify neuron number. The medial prefrontal cortex was examined because it is involved inseveral cognitive tasks and is known to be sensitive to both aging and ovarian hormones. Usingunbiased stereology and light microscopy, neuron number and synaptophysin labeled boutonsiiiwere 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 thet-maze faster than no replacement animals, but there were no differences in performance on thedelayed portion of the task. However, on the Morris water maze, animals receiving this hormonetreatment were impaired as compared to other hormone treated groups. Estrogen in combinationwith MPA resulted in greater synaptophysin levels in the medial prefrontal cortex. Analysis oftyrosine hydroxylase fibers found that animals receiving estrogen in combination with MPAconsistently had significantly higher tyrosine hydroxylase pixel densities than no replacementanimals. Hormone treatment did not significantly alter neuron number in the medial prefrontalcortex.These results indicate that the effects of long-term hormone treatment are task specific and longtermhormone treatments alter dopaminergic functioning and synapse number in the medialprefrontal cortex, providing a possible mechanism by which long-term hormone treatments caninfluence cognition. Importantly, these beneficial neural outcomes were observed in groupsreceiving estrogen in combination with the controversial progestin, MPA.