Basic and translational research that embraces a One Health philosophy is a cornerstone of biomedical science, resulting in breakthrough therapies for animals and people alike. At the Auburn University College of Veterinary Medicine, investigators lead such efforts by pursuing new approaches to the management of pain, treatment of neurogenic hypertension, and understanding the impact of sleep on brain health. Following are a few examples of such research in the College. For more, see www.vetmed.auburn.edu.
Managing chronic pain
Dr. Kristine Griffett studies nuclear receptors, a family of transcription factors that regulate physiological processes in all species. Dr. Griffett leads NIH-funded studies (NIH NINDS R01NS126204; NIH NIAID R03AI177835) to develop nonopioid therapeutics for chronic inflammatory pain targeting REV-ERB nuclear receptors. Working with medicinal and computational chemists, she seeks to discover, synthesize, and characterize new compounds to alleviate chronic pain without the detrimental side effects of current therapies. While NIH-sponsored work is focused on human therapeutics, Dr. Griffett is also evaluating these small molecules for the alleviation of pain in animals and, working with a veterinary neurologist, is testing safety and efficacy in a canine model. The Griffett lab is also investigating how nuclear receptors are involved in cell signaling and disease. The goal is to improve the lives of those suffering from chronic pain, whether human or animal.
Advancing treatments for neurogenic hypertension and Alzheimer disease
Drs. Griffett and Vinicia Biancardi joined forces to explore whether REV-ERB is a therapeutic target for neurogenic hypertension—a form of hypertension that originates in the CNS and is resistant to current pharmacological interventions. Recently, this team discovered a link between the renin-angiotensin system signaling via angiotensin II and a loss of REV-ERB expression in hypertensive rats. In humans, hypertension is a major risk factor for the development of Alzheimer disease (AD) and AD-like cognitive dysfunction. Using animal models and innovative pharmacological approaches, the team is exploring how neurogenic hypertension leads to cognitive dysfunction and whether targeting REV-ERB can prevent the onset of AD. Understanding these cellular processes will facilitate the development of new therapies to promote quality of life and advance One Health.
Reactive microglia and astrocytes often induce neuroinflammation in chronic pain, hypertension, and AD models.
Citation: American Journal of Veterinary Research 84, 12; 10.2460/ajvr.23.09.0219
Chemogenetic activation of sleep circuitry in AD
AD is a neurodegenerative disease leading to debilitating cognitive decline. Currently, there is no cure and there are few disease-modifying treatments for AD. Poor sleep is a commonly reported symptom in AD, preceding cognitive decline. A link between poor sleep and soluble β-amyloid (Aβ), an early AD marker, was recently described. Increased Aβ leads to impairments in sleep while impaired sleep increases Aβ accumulation. Dr. Daniel Kroeger leads efforts to determine whether increasing the amount of sleep during early stages of AD can break this cycle and modify or halt disease progression, preventing cognitive decline. In a mouse model of AD, he uses chemogenetics to stimulate specific sleep-active neurons to improve sleep. If improved sleep reduces AD biomarker burden and prevents cognitive decline, the results will reinforce the importance of treating sleep disorders, especially in populations vulnerable to AD.
