The Structure and Function of the Honeybee Blood-Brain Barrier

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Description
Many animals possess a blood-brain barrier, which is a layer of cells that restricts the passage of molecules into the central nervous system. The primary function of the blood-brain barrier is to preserve ionic homeostasis within the brain; however, it…

Many animals possess a blood-brain barrier, which is a layer of cells that restricts the passage of molecules into the central nervous system. The primary function of the blood-brain barrier is to preserve ionic homeostasis within the brain; however, it is also responsible for selectively importing an array of nutritional and signaling molecules to support brain function and for exporting metabolic waste. Across the species in which it has been studied, the structure and function of the blood-brain barrier dynamically regulates the interaction between the brain and peripheral physiological systems. Honeybee (Apis mellifera) workers are a firmly established neurobiological model which can be utilized to answer questions about the physiological and environmental mechanisms that regulate central nervous system health and behavior. It is likely that the honeybee blood-brain barrier plays an important role mediating the interactions between the brain and its environment, however, the blood-brain barrier is largely unconsidered in the realm of honeybee neurobiological research. In this dissertation, I provide the first in depth characterizations of the structure and function of the honeybee blood-brain barrier. First, I characterized the ultrastructural organization of the honeybee blood-brain barrier. The results of this study demonstrate its structural heterogeneity, including how this heterogeneity compares between two age groups. Next, I assessed two dimensions of blood-brain barrier permeability among three honeybee age groups and among honeybees exposed to varying amounts of infestation with the parasitic mite Varroa destructor. This study demonstrated that paracellular permeability has greater resilience than transcellular permeability, the latter of which is particularly increased by a high parasitic load. Finally, I developed a novel technique combining stable isotope labelling and Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) to demonstrate that the large, pro-social protein vitellogenin is able to cross the honeybee blood-brain barrier into the brain. Together, these studies represent the first in-depth analysis of the honeybee blood-brain barrier, establishing new directions for understanding the regulation of honeybee health, disease, and behavior.
Date Created
2024
Agent

Say Cheese! Finding the Correlation Between the Structure and Function of Ovaries using Histology

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Description
Histology, the microscopic examination of tissues, is a pivotal tool in research. By providing a detailed view of cellular structures and their organization, this technique allows researchers to advance knowledge in many different disciplines including women’s health and ovarian studies.…

Histology, the microscopic examination of tissues, is a pivotal tool in research. By providing a detailed view of cellular structures and their organization, this technique allows researchers to advance knowledge in many different disciplines including women’s health and ovarian studies. Studying the female reproductive system is of utmost importance due to its multifaceted effects on aspects such as biological functions, cellular mechanisms, and complex behavioral patterns in women. Therefore, the aim of this honors thesis is to refine and adapt a set of protocols from the Mayer-Dyer Laboratory for ovarian and follicular processing so that they are optimal to use in the Bimonte-Nelson Laboratory of Memory and Aging in the Department of Psychology at Arizona State University. The subsequent aim for the thesis is to replicate and extend the new protocols to complete histology of the ovaries from an interdisciplinary study that evaluated the consequences of hysterectomy with and without estrogen replacement for brain and cognition. This dual-pronged approach will not only contribute to the ongoing discussion regarding the effects of hysterectomy, but also provides a valuable framework for future research endeavors in the field.
Date Created
2024-05
Agent

Examining Social Hierarchies Using a Novel Dominance Apparatus

Description
Discovering more about social hierarchies within groups of mice and the underlying brain mechanisms supporting differences in dominance is essential to understanding social roles and individuality. In this study, we aimed to discover if a novel dominance assay is able…

Discovering more about social hierarchies within groups of mice and the underlying brain mechanisms supporting differences in dominance is essential to understanding social roles and individuality. In this study, we aimed to discover if a novel dominance assay is able to determine social hierarchies in groups of three, as well as how this novel assay compares to a classic dominance tube test. SLEAP software, a machine learning tool, was used to analyze the behaviors of the mice in the novel dominance apparatus. In addition, cytokine levels were collected from the mice to assess possible correlations between hierarchical standing and presence of inflammatory agents.
Date Created
2024-05
Agent

Utilization of Deep Neural Networks to Investigate Sex-Dependent and Cerebellar Modulation
Impacts on Social Behavior in Mice

Description
The cerebellum is recognized for its role in motor movement, balance, and more recently, social behavior. Cerebellar injury at birth and during critical periods reduces social preference in animal models and increases the risk of autism in humans. Social behavior…

The cerebellum is recognized for its role in motor movement, balance, and more recently, social behavior. Cerebellar injury at birth and during critical periods reduces social preference in animal models and increases the risk of autism in humans. Social behavior is commonly assessed with the three-chamber test, where a mouse travels between chambers that contain a conspecific and an object confined under a wire cup. However, this test is unable to quantify interactive behaviors between pairs of mice, which could not be tracked until the recent development of machine learning programs that track animal behavior. In this study, both the three-chamber test and a novel freely-moving social interaction test assessed social behavior in untreated male and female mice, as well as in male mice injected with hM3Dq (excitatory) DREADDs. In the three-chamber test, significant differences were found in the time spent (female: p < 0.05, male: p < 0.001) and distance traveled (female: p < 0.05, male: p < 0.001) in the chamber with the familiar conspecific, compared to the chamber with the object, for untreated male, untreated female, and mice with activated hM3Dq DREADDs. A social memory test was added, where the object was replaced with a novel mouse. Untreated male mice spent significantly more time (p < 0.05) and traveled a greater distance (p < 0.05) in the chamber with the novel mouse, while male mice with activated hM3Dq DREADDs spent more time (p<0.05) in the chamber with the familiar conspecific. Data from the freely-moving social interaction test was used to calculate freely-moving interactive behaviors between pairs of mice and interactions with an object. No sex differences were found, but mice with excited hM3Dq DREADDs engaged in significantly more anogenital sniffing (p < 0.05) and side-side contact (p < 0.05) behaviors. All these results indicate how machine learning allows for nuanced insights into how both sex and chemogenetic excitation impact social behavior in freely-moving mice.
Date Created
2024-05
Agent

How many new friends can a menopausal rat remember? Developing a new task of social recognition with an increasing working memory load

Description
Memory as whole is impacted by changes associated with aging and menopause. Different memory types are often tested preclinically utilizing rats in different task paradigms. Most studies have focused on understanding social recognition or working memory, however these memory types…

Memory as whole is impacted by changes associated with aging and menopause. Different memory types are often tested preclinically utilizing rats in different task paradigms. Most studies have focused on understanding social recognition or working memory, however these memory types have yet to be studied together. This thesis focuses on the process of creating and testing a new social recognition task that incorporates a working memory load. We tested different types of previously used social recognition paradigms with an increasing load and through qualitative and quantitative observations the task was modified until a final task was developed for a social working memory study. Young female rats were tested in this task in progressive, meaning a chronologically increasing load and nonprogressive, meaning non-chronological increase in load cognitions. It was found that young female rats had the ability to distinguish between the familiar and novel conspecifics before memory load exceeded four familiar and one novel conspecifics. Once validated through future studies, this task may be utilized to understand the impact of different types of menopause on social working memory.
Date Created
2024-05
Agent

Spatial Working and Reference Memory in a Rodent Model of Surgical Menopause: Correlations with Uterine Gene Expression

Description
It is well documented that menopause and the related decline in circulatory steroid hormones estrogen and progesterone are associated with memory alterations. Rodent models of surgical menopause can be used to study these effects, including ovariectomy (Ovx), or the surgical…

It is well documented that menopause and the related decline in circulatory steroid hormones estrogen and progesterone are associated with memory alterations. Rodent models of surgical menopause can be used to study these effects, including ovariectomy (Ovx), or the surgical removal of the ovaries. This thesis aimed to characterize the effects of surgical menopause on spatial working and reference memory in rats and examine profiles of uterine gene expression alterations that may serve as indications of mechanisms underlying this association. Eighteen female rats were randomly assigned to one of two surgical treatment groups, either Ovx (the surgical menopause group) or sham (the control group). All subjects underwent testing on the water version of the radial arm maze (WRAM) which allows for the assessment of reference memory errors and two types of working memory errors. After behavioral testing, rat uterine tissues were dissected and RNA sequenced. The results showed that Ovx impaired spatial reference memory performance during a maze learning phase, with Ovx rats making reference memory failures earlier in the day, even before working memory load increased, as compared to control rats. There were no surgical menopause effects on spatial working memory, which may be due to the low working memory load and the young age of the rats. Post-hoc analyses showed that reference memory performance was correlated with nerve growth factor (NGF) and acetylcholinesterase (AChE) gene expression in uterine tissues. These findings add to the literature on the impact of estrogen and female cyclicity on memory and cognition. The results suggest that Ovx impairment of the ability to learn long-term spatial memory information relates to uterine gene expression underlying cellular functioning and that NGF and AChE genes are involved in pathways that give way to underlying cellular functioning that impacts cognition. Future studies should continue to evaluate the effects of menopause on memory function and the effectiveness of hormone therapy.
Date Created
2024-05
Agent

Novel Approaches to Modeling Depression in Female and Male Rats: Highlighting the Significance of Age and Sex Hormones

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Description
Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit…

Research demonstrates that chronic stress produces a depressive-like profile in rodents, affecting several domains including, cognition, depressive-like behavior, and anxiety-like behavior. However, chronic stress leads to these outcomes in a sex-dependent manner, as young adult female rodents fail to exhibit impaired cognition and increased depressive and anxiety-like behavior following chronic stress. The primary goal of this dissertation was to reveal novel elements contributing to female susceptibility to stress-induced depressive-like presentations and possible factors that may counteract such outcomes. In chapter 2, novel stress paradigms were investigated to determine whether more robust stressors would lead to spatial memory deficits and elevated anxiety in young adult female and male rats. Results demonstrated that chronic stress impaired spatial memory in males, while the robust stressors failed to impair spatial memory in females. Chapter 3 revealed that both females and males in chapter 2 showed BLA dendritic hypertrophy days following the stressor without hippocampal alterations, with the latter likely due to the passage of time allowing for restructuring. Consequently, chapters 4 through 6 were conducted to investigate whether females would show chronic stress effects at middle-age in ovariectomized (OVX) females because menopause is a period of high vulnerability to cognitive and depressive-like effects. Chapter 4 investigated whether the stress hormone, corticosterone, would impair spatial working memory and increase the depressive-like profile of OVX, middle-aged female rats, which was confirmed using the radial arm water maze (RAWM), sucrose preference (SP), forced swim test (FST), and elevated plus maze (EPM). Chapter 5 investigated if estradiol (E2) may prevent the negative valence outcomes induced by OVX in middle-aged female rats. However, E2 showed antidepressant properties during FST, but failed to do so in other behavioral tasks. Chapter 6 further explored E2’s role in mitigating corticosterone-induced effects on cognition and mood in middle-aged female and male rats, with more pronounced antidepressant effects in females. Notably, this chapter unveiled a novel correlation between spatial memory and anxiety-like behavior in corticosterone-treated female rats. Collectively, these studies delineate a corticosterone-based model of depression in female rodents and introduce a novel approach for analyzing variables across multiple behavioral domains.
Date Created
2023
Agent

Using Transgenic Mice (APP/PS1) to Model Alzheimer’s Disease to Understand
Hippocampal-Dependent Memory

Description

Alzheimer’s disease (AD) is an irreversible brain disorder that plagues millions of people with no current cure. Current clinical research is slowly advancing to more definitive treatments in hopes of reducing the effects of progressive cognitive and behavioral decline, but…

Alzheimer’s disease (AD) is an irreversible brain disorder that plagues millions of people with no current cure. Current clinical research is slowly advancing to more definitive treatments in hopes of reducing the effects of progressive cognitive and behavioral decline, but none so far can slow AD’s onset. A brain area known as the nucleus incertus (NI) was recently discovered to potentially impact AD because of its connections to brain targets that degenerate; however, the NI’s role is unknown. This goal of this experiment was to use a transgenic mouse model (APP/PS1) that expresses AD pathology slowly as found in humans, and to test the mice in a variety of cognitive and anxiety assessments. Mice of both sexes and two different ages were used, with the first being young adult before AD pathology manifests (around 3-4 months old), and the second being around the cusp of when AD pathology manifests (late adult, 8-10 months old). The mice were tested in a variety of cognitive tasks that included the novel object recognition (NOR), Morris water maze (MWM), and the object placement (OP), with the latter being the focus of my thesis. Anxiety measures were taken from the open field (OF) and elevated plus maze (EPM) with the visible platform (VP) used to ensure mice could perform on the rigorous MWM task. In the OP, we found an age effect, where the older mice were less likely to explore the moved object during the OP compared to the younger mice; motor ability was unlikely to explain this effect. We did not find any significant age by genotype effects. These findings indicate that cognitive impairment only just started to affect the older cohort, since OP impairment was found on one measure and not another. Other measures currently being quantified will be helpful in understanding this data, and to see whether learning, memory, and anxiety are affected.

Date Created
2023-05
Agent

The Importance of Studying Interactions With Ovarian Hormones: Implications for Depressive Symptoms in Premenopausal and Menopausal Women

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Description

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in…

The relevance of depression in the clinical realm is well known, as it is one of the most common mental disorders in the United States. Clinical depression is the leading cause of disease for women worldwide. The sex difference in depression and anxiety has guided the research of not just recent studies but older studies as well, supporting the theory that gonadal hormones are associated with the mechanisms of emotional cognition. The scientific literature points towards a clear correlative relationship between gonadal hormones, especially estrogens, and emotion regulation. This thesis investigates the neural pathways that have been indicated to regulate mood and anxiety. Currently, the research points to the hypothalamic-pituitary-adrenal axis, which regulates the stress response through its ultimate secretion of cortisol through the adrenal cortex, and its modulated response when exposed to higher levels of estrogen. Another mechanism that has been investigated is the interaction of estrogen and the serotonergic system, which is noteworthy because the serotonergic system is known for its importance in mood regulation. However, it is important to note that the research seeking to determine the neurobiological underpinnings of estrogen and the serotonergic system is not expansive. Future research should focus on determining the direct relationship between cortisol hypersecretion and estrogens, the specific neurobiological effects of serotonergic receptor subtypes on the antidepressant actions of estrogens, and the simultaneous effects of the stress and serotonergic systems on depressive symptoms.

Date Created
2021-05
Agent

Deficits in Spatial Working Memory Depend on Age in a Novel Rat Model of Alzheimer's Disease

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Description
There are currently no disease-modifying treatments to halt or attenuate the progression of Alzheimer’s disease (AD). Transgenic rodent models have provided researchers the ability to recapitulate particular pathological and symptomological events in disease progression. Complete reproduction of all features of…

There are currently no disease-modifying treatments to halt or attenuate the progression of Alzheimer’s disease (AD). Transgenic rodent models have provided researchers the ability to recapitulate particular pathological and symptomological events in disease progression. Complete reproduction of all features of AD in a rodent model has not been achieved, potentially lending to the inconclusive treatment results at the clinical level. Recently, the TgF344-AD transgenic rat model has started to be evaluated; however, it has not been well characterized in terms of its cognition, which is fundamental to understanding the trajectory of aging relative to pathology and learning and memory changes. Therefore, the aim of the current study was to identify cognitive outcomes at 6, 9, and 12 months of age in the TgF344-AD rat model. Sixty female transgenic (Tg) and wildtype (WT) rats were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. Results from the asymptotic phase of the water radial arm maze showed that the 6 mo-Tg animals had marginally impaired working memory compared to 6 mo-WT rats, and 12 mo-Tg rats had significantly impaired working memory compared to 12 mo-WT rats. The 9 mo-Tg animals did not demonstrate a significant difference in working memory errors compared to the 9 mo-WT animals. This pattern of impairment, wherein Tg animals made more working memory errors compared to WT animals at the 6 and 12 month time points, but not at the 9 month time point, may be indicative of an inflammatory response that proves helpful at incipient stages of disease progression but eventually leads to further cognitive impairment. These results provide insight into the potential earliest time point that prodromal cognitive symptoms of AD exist, and how they progress with aging. Brain tissue was collected at sacrifice for future analyses of pathology, which will be used to glean insight into the temporal progression of pathological and cognitive outcomes.
Date Created
2020-05
Agent
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