Heather Bimonte-Nelson

Heather Bimonte-Nelson
Arizona State University | ASU · Department of Psychology

Ph.D.

About

106
Publications
9,842
Reads
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Introduction
The research goals of our laboratory are to characterize the cognitive and brain changes that occur during aging, as well as to develop strategies to attenuate these age-related alterations. Towards this goal, one of our primary interests is to determine the roles that endogenous and exogenous steroids play in the brain and cognition during aging in females. Our overarching aim is to optimize the trajectory of hormonal and cognitive change as related to different menopause types.
Additional affiliations
July 2005 - present
Arizona State University
Position
  • Associate Professor, Behavioral Neuroscience Division Chair
January 2001 - June 2005
Medical University of South Carolina
Position
  • PostDoc Position

Publications

Publications (106)
Article
Full-text available
Women report greater cigarette cravings during the menstrual cycle phase with higher circulating levels of 17β-estradiol (E2), which is metabolized to estrone (E1). Both E2 and E1 bind to estrogen receptors (ERs), which have been highly studied in the breast, uterus, and ovary. Recent studies have found that ERs are also located on GABAergic medium...
Article
Full-text available
Oral contraceptives and hormone therapies require a progestogen component to prevent ovulation, curtail uterine hyperplasia, and reduce gynecological cancer risk. Diverse classes of synthetic progestogens, called progestins, are used as natural progesterone alternatives due to progesterone’s low oral bioavailability. Progesterone and several synthe...
Preprint
The TgF344 rat model of Alzheimer’s disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A β ) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The...
Article
Full-text available
A major obstacle to progress in understanding the etiology of normative and pathological human brain aging is the availability of suitable animal models for experimentation. The present article will highlight our current knowledge regarding human brain aging and neurodegeneration, specifically in the context of Alzheimer’s disease (AD). Additionall...
Article
Women have more difficulty maintaining smoking cessation than men, and experience greater withdrawal symptomatology as well as higher prevalence of relapse. Further, currently available treatments for smoking cessation, such as the nicotine patch and varenicline, have been shown to be less effective in women. Fluctuations in ovarian hormones across...
Article
Full-text available
A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, includin...
Article
Menopause has been linked to changes in memory. Estrogen‐containing hormone therapy is prescribed to treat menopause‐related symptoms and can ameliorate memory changes, although the parameters impacting estrogen‐related memory efficacy are unclear. Cognitive experience and practice have been shown to be neuroprotective and to improve learning and m...
Article
Menopause-associated and hormone-associated cognitive research has a rich history built from varied disciplines and species. This review discusses landmark rodent and human work addressing cognitive outcomes associated with varied experiences of menopause and hormone therapy. Critical variables in menopause and cognitive aging research are consider...
Article
Full-text available
Rodent aging research often utilizes spatial mazes, such as the water radial-arm-maze (WRAM), to evaluate cognition. The WRAM can simultaneously measure spatial working and reference memory, wherein these two memory types are often represented as orthogonal. There is evidence, however, that these two memory forms yield interference at a high workin...
Article
Full-text available
Exogenously administered 17β-estradiol (E2) can improve spatial learning and memory, although E2 also exerts undesired effects on peripheral organs. Clinically, E2 has been solubilized in cyclodextrin for intranasal administration, which enhances brain-specific delivery. Prior work shows that the cyclodextrin structure impacts region-specific brain...
Article
Full-text available
Hormone therapy that contains 17β-estradiol (E2) is used commonly for treatment of symptoms associated with menopause. E2 treatment has been shown to improve cognitive function following the decrease in ovarian hormones that is characteristic of menopause. However, once in circulation, the majority of E2 is bound to serum hormone binding globulin o...
Article
17β-estradiol (E2)-containing hormone therapy is a safe, effective way to alleviate unwanted menopause symptoms. Preclinical research has focused upon the role of E2 in learning and memory using a surgically menopausal rodent model whereby the ovaries are removed. Given that most women retain their reproductive tract and undergo a natural menopause...
Article
Full-text available
Discovery of neural mechanisms underlying neuropsychiatric disorders within the aging and addiction fields has been a main focus of the National Institutes of Health. However, there is a dearth of knowledge regarding the biological interactions of aging and addiction, which may have important influences on progression of disease and treatment outco...
Chapter
Increasing evidence has demonstrated that sex steroid hormones, such as estrogens and progestogens, impact nonreproductive behaviors such as cognitive function in women and nonhuman animals. In addition to cognitive alterations associated with the reproductive cycle in young females, endocrine changes in middle-aged and aged females can impact cogn...
Article
The influence of estrogens on modifying cognition has been extensively studied, revealing that a wide array of factors can significantly impact cognition, including, but not limited to, subject age, estrogen exposure duration, administration mode, estrogen formulation, stress history, and progestogen presence. Less known is whether long-term, exten...
Article
Changes in pituitary-ovarian hormones across the menopausal transition have multiple physiological consequences. However, little is known about how the major types of post-menopausal hormone therapy (HT) affect pituitary-ovarian hormonal relationships. This study evaluated these relationships in recently menopausal women (52.45± 2.49 years of age)...
Article
Full-text available
RASopathies are a family of related syndromes caused by mutations in regulators of the RAS/Extracellular Regulated Kinase 1/2 (ERK1/2) signaling cascade that often result in neurological deficits. RASopathy mutations in upstream regulatory components, such as NF1, PTPN11/SHP2, and RAS have been well-characterized, but mutation-specific differences...
Data
Juvenile Raf1L613V/wt cortices show normal extent of myelination. A-D: Representative double immunolabeled sections of P14 sensory cortex for MBP and DAPI showed no qualitative differences in the pattern of myelination between control (A, B) and mutant (C, D) cortices (scale bar = 50μm). (TIF)
Article
Full-text available
Women report greater craving during certain phases of the menstrual cycle. As well, research indicates that pharmacotherapies for smoking may be less efficacious in women compared to men, which may be due to interactions with natural fluctuations in ovarian hormone levels. N-Acetylcysteine (NAC) is a glutamatergic compound that has shown some effic...
Article
Full-text available
Approximately one-third of women experience hysterectomy, or the surgical removal of the uterus, by age 60, with most surgeries occurring prior to the onset of natural menopause. The ovaries are retained in about half of these surgeries while, for the other half, hysterectomy occurs concurrently with oophorectomy. The dogma is that the non-pregnant...
Article
Full-text available
Enzastaurin is a Protein Kinase C-β selective inhibitor that was developed to treat cancers. Protein Kinase C-β is an important enzyme for a variety of neuronal functions; in particular, previous rodent studies have reported deficits in spatial and fear-conditioned learning and memory with lower levels of Protein Kinase C-β. Due to Enzastaurin’s me...
Article
With menopause, circulating levels of 17β-estradiol (E2) markedly decrease. E2-based hormone therapy is prescribed to alleviate symptoms associated with menopause. E2 is also recognized for its beneficial effects in the central nervous system (CNS), such as enhanced cognitive function following abrupt hormonal loss associated with ovariectomy. For...
Article
Female mammals undergo natural fluctuations in sex steroid hormone levels throughout life. These fluctuations span from early development, to cyclic changes associated with the menstrual or estrous cycle and pregnancy, to marked hormone flux during perimenopause, and a final decline at reproductive senescence. While the transition to reproductive s...
Article
Full-text available
Decreased serotonin (5-HT) function is associated with numerous cognitive and affective disorders. Women are more vulnerable to these disorders and have a lower rate of 5-HT synthesis than men. Serotonergic neurons in the dorsal raphe nucleus (DRN) are a major source of 5-HT in the forebrain and play a critical role in regulation of stress-related...
Article
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 di...
Article
Many studies suggest sex differences in memory and hippocampal size, and that hormone therapy (HT) may positively affect these measures in women; however, the parameters of HT use that most likely confer benefits are debated. We evaluated the impact of sex and postmenopausal HT use on verbal learning and memory and hippocampal size in 94 cognitivel...
Article
Introduction: For decades, progestins have been included in hormone therapies (HT) prescribed to women to offset the risk of unopposed estrogen-induced endometrial hyperplasia. However, the potential effects on cognition of subcategories of clinically used progestins have been largely unexplored. Methods: In two studies, the present investigatio...
Article
Prenatal stress and overexposure to glucocorticoids (GC) during development may be associated with an increased susceptibility to a number of diseases in adulthood including neuropsychiatric disorders, such as depression and anxiety. In animal models, prenatal overexposure to GC results in hyper-responsiveness to stress in adulthood, and females ap...
Article
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 bi...
Article
The field of how learning and remembering happens in the brain has a rich history. We have made considerable discoveries thus far; however, there is still much left to discern. Questions regarding the search for the engram, or memory trace, have persisted through the decades, and this research area is on a fast trajectory forward. In fact, like man...
Article
How does learning and remembering happen? The answer to this question gives us a lot to talk about. Indeed, we are now in an exciting time of science when technological advances in the neuroscience fi eld are meeting the demands and eagerness of scientists who wish to study relationships between the brain and cognition. Learning and memory experime...
Article
This protocol provides the information necessary to experimentally test rodents on a water escape radial-arm maze task assessing working and reference memory simultaneously. Apparatus setup, testing items needed, step-by-step test procedures, testing score sheets, performance quantification procedures, and troubleshooting are specified, detailed, a...
Chapter
This protocol provides the information necessary to experimentally test rodents on the Morris maze task assessing spatial reference memory. Apparatus setup, step-by-step test procedures, and performance quantification procedures are specified, detailed, and discussed. Examples of peer-reviewed published research literature using these procedures ar...
Chapter
This protocol provides the information necessary to experimentally test rodents on the visible platform task, which assesses competence to perform a water escape task. Apparatus setup, step-by-step test procedures, and performance quantification procedures are specified, detailed, and discussed. Examples of peer- reviewed published research literat...
Chapter
This protocol provides the information necessary to experimentally test rodents on water escape maze tasks to assess various forms of memory. Room and cue setup, testing items needed, common rodent behavior examples, practical advice, and troubleshooting are detailed and discussed.
Article
Full-text available
In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the maternal amnesia phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx) rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GAB...
Article
Full-text available
Editor's summary: Estrogen prodrug protects the brain Although estrogen is considered to heal the brain of many neurological and psychiatric symptoms, targeting the hormone to the brain only—and avoiding activity in other tissues—is no trivial feat. Prokai et al. discovered a “prodrug,” called DHED (10β, 17β-dihydroxyestra-1,4-dien-3-one), that i...
Article
Estrogens impact the organization and activation of the mammalian brain in both sexes, with sex-specific critical windows. Throughout the female lifespan estrogens activate brain substrates previously organized by estrogens, and estrogens can induce non-transient brain and behavior changes into adulthood. Therefore, from early life through the tran...
Article
Full-text available
Here, we show that a small-molecule bioprecursor, 10β,17β-dihydroxyestra-1,4-dien-3-one, converts to 17β-estradiol in the brain after systemic administration, but remains inert in the rest of the body. The localized and rapid formation of estrogen from the bioprecursor in the brain was revealed by a series of in vivo bioanalytical assays and throug...
Chapter
This protocol provides the information necessary to experimentally test rodents on a delayed match to sample task assessing working and recent memory. Procedures are also discussed for extended delay testing to evaluate memory retention at different time intervals. Apparatus setup, step-by-step test procedures, testing score sheets, and performance...
Article
Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ra...
Chapter
Reproductive hormones such as estrogens, androgens, progesterone, and others are responsible for the regulation of countless body functions in addition to their well-known control over reproductive function and behavior. The list of processes governed by internal hormonal secretions is extensive and, as such, hormonal fluctuations influence how ani...
Chapter
Full-text available
This chapter describes several best practices for collecting, storing, analyzing, and writing up data generated from biobehavioral research. The goal is to provide a foundation for researchers who wish to consider more advanced topics of experimental design and statistical inference in their work. The principles considered here are general and appl...
Article
Full-text available
We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive te...
Article
Androstenedione, the main circulating ovarian hormone present after menopause, has been shown to positively correlate with poor spatial memory in an ovary-intact rodent model of follicular depletion, and to impair spatial memory when administered exogenously to surgically menopausal ovariectomized rats. Androstenedione can be converted directly to...
Article
Introduction: This study examines individual differences in navigational strategy to test and translate between active spatial reasoning models in human and rodent research. We built a real-world, 50-foot diameter, 11-arm walk-through Human Radial-Arm Maze (HRAM) to parallel the Rodent Radial-Arm Maze (RRAM). Methods: 157 participants performed the...
Article
Full-text available
Background HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. Howeve...
Article
Understanding the cognitive impact of endogenously derived, and exogenously administered, hormone alterations is necessary for developing hormone treatments to support healthy brain function in women, especially during aging. The increasing number of studies in the burgeoning area of translational cognitive neuroendocrinology has revealed numerous...
Conference Paper
Recently, our laboratory found that the main circulating hormone present after menopause and follicle depletion, androstenedione, impairs memory. Specifically, we evaluated two doses of exogenously administered androstenedione to middle-aged ovariectomized rats. Results showed that androstenedione, at the highest dose, impaired working and referenc...
Article
Full-text available
Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, the fixed-minimum interval schedule of reinforcement, or FMI), and workin...
Article
Full-text available
Nutrition has been highlighted as a potential factor in Alzheimer's disease (AD) risk and decline and has been investigated as a therapeutic target. Broad-based combination diet therapies have the potential to simultaneously effect numerous protective and corrective processes, both directly (e.g., neuroprotection) and indirectly (e.g., improved vas...
Article
After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle-depleted ovaries. In two independent studies, in rodents that had undergone ovarian follicular depletion, we found that higher endogenous serum androstenedione levels correlated with increased working memory errors. This led to the hypoth...
Article
Full-text available
M(1) muscarinic acetylcholine receptors (mAChRs) represent a viable target for treatment of multiple disorders of the central nervous system (CNS) including Alzheimer's disease and schizophrenia. The recent discovery of highly selective allosteric agonists of M(1) receptors has provided a major breakthrough in developing a viable approach for the d...
Article
CEE (conjugated equine estrogens) is the most widely prescribed estrogen-only menopausal hormone therapy in the United States, and is comprised of over 50% estrone (E1) sulfate. Following CEE administration, E1 is the principal circulating estrogen. However, the cognitive and neurobiological effects of E1 in a middle-aged rodent model have not yet...
Article
Chronic stress results in reversible spatial learning impairments in the Morris water maze that correspond with hippocampal CA3 dendritic retraction in male rats. Whether chronic stress impacts different types of memory domains, and whether these can similarly recover, is unknown. This study assessed the effects of chronic stress with and without a...
Thesis
Full-text available
Cognitive function is multidimensional and complex, and research indicates that it is impacted by age, lifetime experience, and ovarian hormone milieu. One particular domain of cognitive function that is susceptible to age-related decrements is spatial memory. Cognitive practice can affect spatial memory when aged in both males and females, and in...
Article
The synthetic progestin medroxyprogesterone acetate (MPA), widely used in hormone therapy (HT) and as the contraceptive Depo Provera, is implicated in detrimental cognitive effects in women. Recent evidence in aged ovariectomized (Ovx) rodents shows that short-term MPA treatment impairs cognition and alters the GABAergic system. Using rats, we eval...
Article
Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are decl...