Overview
Broadly speaking, my research interests lie in determining how lifestyle factors affect brain health and influence the risk of diseases with a neurobiological basis, including neuropsychiatric and neurodegenerative diseases. Unfortunately, many of these diseases, such as addiction, mood disorders (anxiety, depression), and Alzheimer’s disease, lack cures or even treatments that are universally highly effective. Therefore, investigation of these modifiable lifestyle factors is vital not only to determine if they can be used to prevent and/or treat brain-based diseases, but also how, as doing so may allow us to identify novel targets for treatment. Additionally, I am interested in identifying medications that may be repurposed for dementia, and how biological factors, such as an individual’s sex and the aging process, may influence responses to both lifestyle and pharmacological interventions. Many of the aforementioned conditions exhibit a sex bias, with females being more susceptible than males. This research may therefore help pave the way for sex-specific medicine. My research has sought to answer these questions primarily using rodent models, behavior testing, neuroimaging, and molecular biology techniques. For the most up-to-date list of my publications, please visit PubMed or Google Scholar.
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Areas of interest
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Effects of high fat diet/metabolic disease on normal and pathological aging.
Taking a new direction in exploring the role of modifiable lifestyle factors in mouse models of aging and dementia, I have also investigated sex differences in the effects of high fat diet and metabolic disease. Utilizing mouse models of healthy aging, Alzheimer’s disease, vascular dementia, and multi-etiology dementia (combined Alzheimer’s and vascular dementia pathology), a major line of my research has found that high fat diet and metabolic disease preferentially affects females across the lifespan. Ultimately, females tend to exhibit greater susceptibility to dementia pathology, exacerbated by high fat diet/metabolic disease, which may contribute to the increased risk of dementia in women, particularly in the presence of comorbid metabolic disease (Salinero, Robison et al., 2019, FASEBJ; Gannon*, Robison* et al., 2022, J Neuroinflammation). We found that females become more cognitively impaired by high fat diet and that they are uniquely susceptible to cerebrovascular dysfunction, neuroinflammation, and impaired adult hippocampal neurogenesis (Robison et al., 2020, eNeuro; Robison et al., 2020, J. Neuroinflammation; Salinero, Robison et al., 2020, FASEBJ). We also found evidence to suggest that high fat diet sex-dependently alters microglia in the hippocampus, which could be driving the aforementioned differences in diet-induced changes in neurogenesis (Robison et al., 2020, eNeuro). Our lab at NSU is currently looking into mechanisms driving these sex-specific effects, pharmacological interventions capable of reversing them, and sex-specific effects of other diet interventions, such as a clinically-relevant ketogenic diet. This work is funded by NSU College of Psychology Faculty Research Fellowship and NSU Farquhar Honors College. Collaborative projects funded by NINDS are testing novel pharmacological interventions in rodent AD models, incorporating sex and metabolic status as key biological variables as they can influence responses to treatments.
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Pharmacological and non-pharmacological interventions for the prevention/treatment of cerebral amyloid angiopathy.
Cerebral amyloid angiopathy (CAA) is the buildup of toxic protein (most often beta-amyloid) around the blood vessels in the brain. CAA can cause vascular dementia, increases risk of stroke, and contributes to Alzheimer's disease. There are currently no known treatments for CAA, despite the huge burden it creates due to an increasingly aging population. Exercise has been shown to protect against dementia and cognitive decline in aging humans and improve pathology and behavioral deficits in mouse models. Most previous rodent studies, however, utilized a relatively short intervention period and a single “dose” of exercise - often unlimited running wheel access - resulting in large volumes of exercise that are not clinically relevant. By varying length of daily access to a running wheel, I found dose-dependent effects of long-term voluntary wheel running on physiology, cognition/behavior, and neurobiology/pathology in wild-type mice and two different mouse models of dementia, including cerebral amyloid angiopathy (CAA) (Robison et al., 2019, J. Neuroinflammation; Robison et al., Physiol. Behav.; Francis, Robison et al., 2020, J. Alzheimers Dis.). Additionally, I investigated the influence of environmental enrichment in mouse models of healthy aging and CAA. In line with clinical findings, I determined that there were additive beneficial effects of these lifestyle factors and parsed out the unique contributions of various aspects of the traditional enriched environment paradigm most often used in rodent studies (Robison et al., 2020, Int. J. Mol. Sci.). This work also, for the first time, tested the efficacy of modifiable lifestyle factors in the Tg-SwDI mouse model of cerebral amyloid angiopathy, which develops amyloid pathology around blood vessels in the brain (Robison et al., 2020, Int. J. Mol. Sci.; Robison et al., 2019, J. Neuroinflammation). Ongoing work in this area in our lab at NSU is investigating effects of other environmental factors and repurposed cardiovascular medications for the prevention/treatment of CAA. This work is currently funded by the American Heart Association, and the NSU College of Psychology Faculty Research Fellowship.
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Mechanisms of CNS injury contributions to dementia.
Traumatic brain injury (TBI) is a condition in which normal brain function is impaired by an external force. TBI is estimated to affect ~69 million people worldwide each year. Mild TBI’s are the most common form of brain injury (~70-90% of all cases), characterized by little-to-no time unconscious and minimal observable deficits immediately post-injury. Mild brain injuries are commonly attributed to participation in contact sports (e.g. boxing, football, soccer, hockey), military service, and as a result of intimate partner violence. Even mild TBI, especially following repeated injuries, has devastating acute and long-term consequences, including an increased risk of stroke and dementia. Given the clear evidence that TBI increases the risk of dementia in later life, it is of great interest to determine the mechanisms that drive the relationship between different types of TBIs and various dementia-associated neuropathologies, so that targets for intervention may be identified. Ongoing work in this area is examining the effects of repeated mild traumatic brain injury in rodent models of dementia. This work is currently funded by the National Institute on Aging,
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Non-cognitive symptoms of Alzheimer's disease and associated neuropathology.
Although cognitive impairment and associated brain regions (e.g., hippocampus, cortex) have been most widely studied, there are numerous non-cognitive symptoms and associated areas of the brain affected that are commonly observed in Alzheimer’s disease. Further exploration of these phenomena is necessary to prevent and/or treat non-cognitive complications of Alzheimer’s, which may further aggravate disease progression, contribute to poor quality of life, and may even be life-threatening. The hypothalamus is a set of nuclei within the brain that help maintain the body’s internal balance, including the regulation of feeding behavior, metabolism, and maintenance of body weight. Hypothalamic dysfunction occurs early in the clinical course of Alzheimer’s, likely contributing to disturbances in feeding behavior and metabolic function that are often observed years prior to the onset of cognitive symptoms. In a recently published paper, we found marked sex differences in metabolic outcomes of Alzheimer’s mice both on control and high fat diet, which may be representative of two metabolic phenotypes associated with Alzheimer’s disease. In Alzheimer’s females, we see a dramatic increase in susceptibility to some metabolic effects of high fat diet associated with increased caloric intake and decreased energy expenditure, as well as hyperleptinemia, that is associated with severe increases in reactive astrocytes in the hypothalamus. In contrast, males appear to represent an energy deficit state not associated with reduced caloric intake or increased activity levels, with attenuated body weight, hypoleptinemia, increased expression of orexigenic hormones, and high-grade systemic and hypothalamic inflammation (Robison et al., 2020, J. Neuroinflammation). Ongoing work with Dr. Kristen Zuloaga's lab is investigating these findings further in a cross-sectional aging study.
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Effects of reproductive and parental experience in rodent models of healthy and pathological brain aging.
Research suggests that there is a complex and multifaceted relationship between reproductive and maternal experiences and brain health. Pregnancy induces significant hormonal and neurobiological changes in the brain. These changes, such as alterations in gray matter volume and connectivity patterns, are thought to support the development of maternal behaviors and adaptations to motherhood. Motherhood is also associated with enhanced neuroplasticity, particularly in brain regions involved in social cognition, empathy, and caregiving. While pregnancy and motherhood may lead to temporary cognitive changes such as forgetfulness and reduced attention, there's limited evidence to suggest that these changes persist long-term or have significant negative effects on overall cognitive function. The long-term effects of reproductive and maternal experiences on brain health are still not fully understood. Longitudinal studies are needed to investigate how these experiences impact brain aging, cognitive function, and the risk of neurodegenerative diseases later in life. Some studies suggest that experiencing pregnancy and motherhood may have long-term protective effects against certain neurological disorders, such as Alzheimer's disease. The hormonal changes associated with pregnancy, particularly estrogen, may play a role in this protective effect. However, results are mixed, and may depend on a number of factors such as number of children and geographical location. These findings suggest that reproductive and maternal experiences can have significant effects on brain structure and function, both during pregnancy and in the postpartum period. Further research is needed, particularly in animal models, to fully understand the complex interplay between reproductive experiences and brain health across the lifespan. Our current work is investigating the effects of reproductive/maternal experience, as well as later-age interactions with young, on the progression of dementia-related symptoms and pathology in mouse models. This work is funded by the Florida Department of Health.
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Effects of chronic methylphenidate on physiology, behavior, and neurobiology.
Methylphenidate (MP; Ritalin) is a psychostimulant prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). I assisted in the development of the first oral MP dosing paradigm in rodents that closely mimics the pharmacokinetic profile of MP treatment in humans (Thanos, Robison et al., 2015, Pharmacol. Biochem. Behav.). This study and follow-up studies found substantial physiological and behavioral effects of chronic treatment, noting marked sex differences, such that females were more sensitive to the effects of the drug compared to males (Robison et al., 2017, Front. Behav. Neurosci.; Thanos, Robison et al., 2015, Pharmacol. Biochem. Behav.). This is an important finding, considering that the prescription rate of ADHD medications in females has increased more than 500% over the last decade. Additionally, I found that MP has significant effects on dopamine-related neurochemistry and microglial activation in the hippocampus, cortex, thalamus, and basal ganglia (Robison et al., 2018, J. Neural Transm.; Carias et al., 2018, J. Neural Transm.).
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Effects of exercise on drug-seeking behavior and reward-related neurobiology.
Epidemiological and experimental clinical studies have shown promise for using exercise to combat substance use disorders (SUDs). Additionally, animal studies reveal that exercise is protective against the initiation, escalation, extinction, and relapse of substance use of several drug classes (alcohol, nicotine, stimulants, and opiates), and also affects behaviors involved in addiction, including those related to reward, learning and memory, inhibitory control, and stress reactivity and mood. A major area of my research has investigated the ability of aerobic exercise to alter drug-seeking behavior in rodent models. The first experiment found that six weeks of treadmill running decreased cocaine-seeking behavior, and that this effect was greater in males than in females (Thanos et al., 2010, Behav. Brain Res.). Additional studies found that exercise reduced relapse to cocaine seeking behavior triggered by environmental cues and stress (Robison et al., 2018, Behav. Brain Res.; Thanos et al., 2013, Behav. Brain Res.). Follow-up experiments were aimed at exploring possible neurobiological mechanisms driving these behavioral effects. While exercise had no effect on cannabinoid receptors (Swenson et al., 2019; Life Sci.), exercise altered dopamine receptor levels in reward-related brain regions of both sexes in a manner consistent with reduced susceptibility to drug abuse (Robison et al., 2018, Med. Sci. Sports Exerc.). This line of work was featured in U.S. News & World Report and several other news outlets. These findings suggest that fairly small amounts of moderate-intensity exercise may prevent and treat substance abuse and hinted at some of the neurobiological mechanisms driving these changes in behavior. Ongoing work in our lab is investigating the efficacy of chronic forced exercise (treadmill running) for the amelioration of brain changes caused by adolescent binge-drinking. This work is funded by NSU Farquhar Honors College.
