The Elizabeth Byrnes Lab
Opioids and Transgenerational Epigenetic Effects
The increased use and misuse of powerful prescription pain killers, such as Oxycontin®, has resulted in an opioid epidemic impacting men and women of all ages. While the risk of overdose death and addiction-related disease are of primary concern, the long-term impact of increased opioid exposure across such a broad population remains unknown. Increased use in adolescent populations and in pregnant women may be a particular concern. These issues are studied in the lab using two different preclinical models.
Adolescent Opioid Exposure
Our lab uses animal models (mouse and rat) to examine the effects of opioid exposure during adolescent development on future generations. Specifically, we examine how a history of drug use in either the mother or the father can alter the neurodevelopment of future offspring. The mechanisms involved in the transmission of effects from parent to offspring and the stability of these modifications across multiple generations is the primary focus of current studies. In particular, we are interested in the role of epigenetic modifications in the hypothalamus that can impact both metabolic processes and reward-related behaviors, including addiction. These studies may serve as a model of epigenetic mechanism involved in the transfer of experiential information across multiple generations.
Prenatal Oxycodone Exposure and Neonatal Abstinence Syndrome
Our lab uses a model of prenatal oxycodone self-administration (rat) to examine the impact of voluntary drug intake on offspring outcomes. We are currently investigating postnatal measures that can be effectively used to document withdrawal and correlate with adult behaviors. In addition, we study modifications in neurodevelopmental protein expression and how these changes may impact on adult addiction-related behaviors. All studies include assessments of both male and female offspring.
Opioids, miRNAs, and Addiction
It has been widely hypothesized that microRNAs (miRNAs) are key regulators of alterations in gene expression associated with the development of addiction. This powerful gene regulatory system can broadly affect changes in distinct and yet functionally related gene networks. The development of novel strategies to deliver miRNAs into animal models of disease represents a unique opportunity to identify critical regulators of the addiction process in an effort to improve therapeutic approaches to treatment. Our current studies focus on miRNA delivery to select brain regions as a gene therapy for the treatment of addiction. Part of this strategy includes identifying miRNAs over-expressed in extracellular vesicles following drug self-administration, as well as the use of CRISPR-Cas9, and novel nanoparticles to modify responding to addictive drugs, including opioids.
Post-Stroke Depression and Relaxin 3
Stroke is the 4th leading cause of death in the US and one of the leading causes of long-term disability. One outcome often reported in both men and women is the onset of post-stroke depression, although it is more common in women. Post-stroke depression is associated with significant long-term disability and often interferes with rehabilitation efforts. However, in spite of the pervasiveness of post-stroke depression and the negative impact of depression on long-term outcomes, few animal models have investigated the development of depressive-like behaviors post stroke. Relaxin 3 is a highly conserved neuropeptide that modulates a number of behaviors with data suggesting both anxiolytic and anti-depressant properties. Our lab is currently examining the development of post-stroke depression using well-validated measures of anhedonia and effort-based responding in male and female rats. Studies include assessment of sex-specific effects on the relaxin 3 system in response to ischemic stroke and the efficacy of relaxin 3 as a novel therapeutic in post-stroke depression.