Tag: Adrianne Huxtable

Maternal opioids decrease neonatal opioid receptor expression in brain regions controlling breathing

Presenter: Emilee McDonald – Biology

Faculty Mentor(s): Adrianne Huxtable, Robyn Naidoo

Session: (In-Person) Poster Presentation

An understudied population in the opioid crisis are infants exposed to maternal opioids experiencing breathing deficits. Our animal model of maternal opioids demonstrated neonatal breathing deficits after birth, which normalized with age despite continued maternal opioid exposure, suggesting neonatal compensation to this early life opioid stressor. To understand the mechanisms of these breathing deficits, we tested the hypothesis that maternal opioids decrease opioid receptor expression (since opioids activate opioid receptors to exert their effects) in a key brainstem site for breathing. Brainstem immunohistochemistry and confocal microscopy assessed typical developmental changes in neonatal opioid receptor expression after maternal no treatment (control). Opioid receptor expression was highest at postnatal day 0 (P0), when neonates begin breathing, and decreased through P11, a critical maturation period of the nervous system. In neonates after maternal opioids, opioid receptor expression was evaluated at P0 (birth), P4 when neonates still receive opioids through breast milk, and P11 after opioid exposure has ceased. Preliminary data support decreased opioid receptor expression in P0 and P4 neonates after maternal opioids, but a return to control levels at P11. Thus, maternal opioids acutely impair opioid receptor expression in a brainstem site critical for breathing, suggesting opioid receptors may be key to neonatal breathing impairments after maternal opioid exposure.

Systemic Inflammation Increases Expression of Pro-Inflammatory Interleukin-1 Receptors On Neurons And Astrocytes, but Not Microglia, in the Cervical Spinal Cord

Presenter(s): Kelly Royster − Human Physiology

Faculty Mentor(s): Adrianne Huxtable, Austin Hocker

Poster 64

Research Area: Natural/Physical Science

Funding: Adrianne Huxtable’s Parker B. Francis Fellowship, University of Oregon

Inflammation is a component of all diseases, whereby key pro-inflammatory signaling molecules and receptors increase systemically and in the central nervous system (CNS). Systemic inflammation activates astrocytes and microglial cells in many regions of the CNS, which alter neuronal function and lead to behavioral changes. Our work has shown systemic inflammation impairs respiratory function through activation of the pro-inflammatory interleukin-1 receptors (IL-1RI) in the cervical spinal cord, but the roles of different cell types are unknown. To better understand how activation of IL-1RIs undermines breathing, we first need to determine what CNS cell types express IL-1RIs and how systemic inflammation changes IL-1RI expression. Based on the expression of IL-1RIs in other CNS regions, we hypothesized systemic inflammation would increase IL-1RI expression on identified neurons, astrocytes and microglia in the cervical spinal cord. Using immunohistochemistry to fluorescently label cell types and IL-1RIs, we first determined the optimal concentration of the IL-1RI antibody (1:250) by
a dilution series (n=5) in the hippocampus, where IL-1RI was known to be expressed after systemic inflammation. Further, preliminary data (n=2) suggest systemic inflammation increases IL-1RI expression on neurons (labeled by NeuN, 1:500) and astrocytes (labeled by GFAP, 1:500), but not microglia (labeled by Iba1, 1:1000). These results suggest neurons and astrocytes are likely the key cells undermining respiratory function after systemic inflammation. Understanding the mechanisms by which systemic inflammation undermines respiratory function may lead to targeted therapeutic interventions to promote breathing.