The effects of estrogens and hormone replacement therapy on adult hippocampal neurogenesis and cognition in young and middle-aged female rats.

• Main Author: Barha, Cindy
• Language: English
• Published: University of British Columbia 2012
• Online Access: http://hdl.handle.net/2429/43475

In women, age-associated decline in cognitive functioning is associated with the onset of menopause, which is the cessation of ovarian functioning and leads to dramatic reduction in circulating levels of ovarian hormones including estradiol. Estrogens have been implicated as possible therapeutic agents for improving cognition in postmenopausal women and have been linked to neurodegenerative disorders such as Alzheimer’s disease. However, the utility of replacement with estrogens has recently been questioned in the literature. The experiments in this thesis aimed to determine the effects of replacement with different estrogens on hippocampus-dependent learning and memory and hippocampal neurogenesis in female rats, and whether these effects were dependent on different factors, including length of exposure, type of estrogens, dose of estrogens, type of memory system examined, age of subjects, and previous reproductive experience. The main findings of the experiments presented in this thesis are that hormone replacement therapy and estrone negatively impact hippocampus-dependent learning and memory (Chapters 2 and 4; Barha and Galea, in press; Barha et al., 2010), whereas other estrogens can improve hippocampus-dependent learning and memory (Chapter 4; Barha et al., 2010). Additionally, hormone replacement therapy alters hippocampal neurogenesis and decreases new neuronal activation in the dentate gyrus, which may account for impairments seen in memory functioning (Chapter 2; Barha and Galea, in press). Naturally occurring estrogens also differentially increase cell proliferation in the dentate gyrus in adult and middle-aged female rats (Chapters 3, 5; Barha et al., 2009; Barha and Galea, 2011), and this effect is dependent on previous reproductive experience in middle-aged females (Chapter 5; Barha and Galea, 2011). Thus, taken together the results from these experiments suggest that some estrogens increase while other estrogens decrease hippocampal neurogenesis and hippocampus-dependent learning and memory. These findings have important implications for determining which alternative forms of estrogens to incorporate into hormone therapy treatments in the future. Furthermore, the findings from this thesis provide new insights into our understanding of the mechanisms and function of adult neurogenesis in the female rat.