The Mazes

Bimonte‐Nelson, Heather A.; Daniel, Jill M.; Koebele, Stephanie V.

doi:10.1007/978-1-4939-2159-1_2

Cited by 14 publications

(31 citation statements)

References 60 publications

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“…To evaluate overall WRAM learning across all days, an omnibus repeated measures ANOVA was run to examine the Day main effect (days 2–12) for each of the three error types (WMC, WMI, and RM errors). Next, based on prior publications (Bimonte-Nelson et al, 2015; Braden et al, 2017), WRAM testing days were blocked into three blocks: Days 2–5 (Block 1), Days 6–9 (Block 2), and Days 10–12 (Block 3). Each block was analyzed separately using repeated measures ANOVA for each of the three error types, as done previously (Bimonte-Nelson et al, 2015; Braden et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two

Prakapenka

Hiroi

Quihuis

et al. 2018

Neurobiology of Aging

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Most estrogen-based hormone therapies are administered in combination with a progestogen, such as Levonorgestrel (Levo). Individually, the estrogen 17β-estradiol (E2) and Levo can improve cognition in preclinical models. However, although these hormones are often given together clinically, the impact of the E2 + Levo combination on cognitive function has yet to be methodically examined. Thus, we investigated E2 + Levo treatment on a cognitive battery in middle-aged, ovariectomized rats. When administered alone, E2 and Levo treatments each enhanced spatial working memory relative to vehicle treatment, whereas the E2 + Levo combination impaired high working memory load performance relative to E2 only and Levo only treatments. There were no effects on spatial reference memory. Mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation, which is involved in memory formation and estrogen-induced memory effects, was evaluated in 5 brain regions implicated in learning and memory. A distinct relationship was seen in the E2-only treatment group between mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation in the frontal cortex and working memory performance. Collectively, the results indicate that the differential neurocognitive effects of combination versus sole treatments are vital considerations as we move forward as a field to develop novel, and to understand currently used, exogenous hormone regimens across the lifespan.

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Section: Methodsmentioning

confidence: 99%

Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two

Prakapenka

Hiroi

Quihuis

et al. 2018

Neurobiology of Aging

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“…We and many others have investigated the effects of dose, task-specific effects, type of hormone, menopause type, as well as route, timing, and duration of treatment administration on both brain and behavior in female rodents [43–45, 113–121]. …”

Section: 1 Evaluating Hormones Behavior and Brains In Rodent Menomentioning

confidence: 99%

“…The radial-arm maze and its water variant (water radial-arm maze, WRAM) assess spatial working and reference memory such that animals are tasked with finding several food rewards or hidden platforms that are not replaced within a day (Figure 6). This results in an increasing working memory load as trials progress; animals must remember where not to return after locating the reward within a day [113]. This measure of increasingly taxed working memory is especially key for translational menopause research.…”

Section: 1 Evaluating Hormones Behavior and Brains In Rodent Menomentioning

confidence: 99%

Modeling menopause: The utility of rodents in translational behavioral endocrinology research

2016

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The human menopause transition and aging are each associated with an increase in a variety of health risk factors including, but not limited to, cardiovascular disease, osteoporosis, cancer, diabetes, stroke, sexual dysfunction, affective disorders, sleep disturbances, and cognitive decline. It is often challenging to systematically evaluate the biological underpinnings associated with the menopause transition in the human population. For this reason, rodent models have been invaluable tools for studying the impact of gonadal hormone fluctuations and eventual decline on a variety of body systems. While it is essential to keep in mind that some of the mechanisms associated with aging and the transition into a reproductively senescent state can differ when translating from one species to another, animal models provide researchers with opportunities to gain a fundamental understanding of the key elements underlying reproduction and aging processes, paving the way to explore novel pathways for intervention associated with known health risks. Here, we discuss the utility of several rodent models used in the laboratory for translational menopause research, examining the benefits and drawbacks in helping us to better understand aging and the menopause transition in women. The rodent models discussed are ovary-intact, ovariectomy, and 4-vinylcylohexene diepoxide for the menopause transition. We then describe how these models may be implemented in the laboratory, particularly in the context of cognition. Ultimately, we aim to use these animal models to elucidate novel perspectives and interventions for maintaining a high quality of life in women, and to potentially prevent or postpone the onset of negative health consequences associated with these significant life changes during aging.

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“…Of note, spatial memory necessitates the use of distal, extra-maze cues to solve a task, working memory is a type of short-term memory that needs to be updated, and reference memory is a form of long-term memory that stays constant (Bimonte-Nelson et al, 2015). Following training, subjects were administered VCD or vehicle treatment, and then repeatedly tested on the same water radial-arm maze task over a four-month period during the VCD-induced menopause transition.…”

Section: Introductionmentioning

confidence: 99%

Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory

Koebele

Mennenga

Hiroi

et al. 2017

Hormones and Behavior

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Cognitive changes that occur during mid-life and beyond are linked to both aging and the menopause transition. Studies in women suggest that the age at menopause onset can impact cognitive status later in life; yet, little is known about memory changes that occur during the transitional period to the post-menopausal state. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of perimenopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the trajectory of cognitive change across time with normal aging and aging with transitional menopause via VCD-induced follicular depletion, as well as to evaluate whether age at the onset of follicular depletion plays a role in cognitive outcomes. Animals experiencing the onset of menopause at a younger age exhibited impaired spatial memory early in the transition to a follicle-deplete state. Additionally, at the mid- and post- follicular depletion time points, VCD-induced follicular depletion amplified an age effect on memory. Overall, these findings suggest that the age at the onset of menopause is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study illustrates how age at menopause onset might impact cognition in menopausal women, and provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition period. Hormone therapy during this critical juncture might be especially efficacious at attenuating age- and menopause- related cognitive decline, producing healthy brain aging profiles in women who retain their ovaries throughout their lifespan.

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The Mazes

Cited by 14 publications

References 60 publications

Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two

Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two

Modeling menopause: The utility of rodents in translational behavioral endocrinology research

Cognitive changes across the menopause transition: A longitudinal evaluation of the impact of age and ovarian status on spatial memory

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