1 option
Perinatal opioid exposure alters neuroimmune, epigenetic, and gabaergic function throughout development Julia Renee Ferrante
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Ferrante, Julia Renee, author.
- Language:
- English
- Subjects (All):
- Pharmacology.
- Genetics.
- Public health.
- Neurosciences.
- Immunology.
- 0419.
- 0369.
- 0982.
- 0317.
- 0573.
- Local Subjects:
- Pharmacology.
- Genetics.
- Public health.
- Neurosciences.
- Immunology.
- 0419.
- 0369.
- 0982.
- 0317.
- 0573.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (180 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- As a result of the ongoing opioid epidemic in the United States, rates of maternal opioid use and, subsequently, the number of infants exposed to opioids in utero, has sharply increased. Infants exposed to opioids during gestation are at risk of developing Neonatal Opioid Withdrawal Syndrome (NOWS), a combination of acute somatic withdrawal symptoms. As clinical studies are unable to fully dissociate the influence of confounding environmental factors from the effects of in utero opioid exposure directly, the long-term impacts of NOWS remain unclear. Thus, the development of rodent models has been critical in attempting to elucidate the molecular and behavioral consequences that arise from perinatal opioid exposure and to further understand how these changes may persist throughout development. To study the neurobiological underpinnings of NOWS, the Blendy lab developed a mouse model of perinatal opioid exposure that encompasses the developmental equivalent of a full-term human pregnancy, in which mice receive morphine throughout gestation and for the first two post-natal weeks. The model effectively replicates several features observed in clinical NOWS, including developmental delays and spontaneous opioid withdrawal upon drug cessation.Morphine activates microglia in adult rodents, though it is unknown how perinatal morphine exposure may impact developing microglia, and, further, whether microglia play a role in producing opioid withdrawal symptoms. Using this morphine exposure paradigm, I found that microglia are increased during morphine exposure but are normalized following spontaneous withdrawal. Pharmacological depletion of microglia during the neonatal period reduced somatic signs of opioid withdrawal, indicating microglia are implicated in the development of perinatal withdrawal. Microglia are involved with both immune signaling and synaptic pruning, prompting further investigation into how these systems may be impacted by morphine exposure during development. I found that perinatal morphine exposure induces persisting suppression within the immune system, characterized by a reduction in brain and peripheral cytokines and a blunted sickness response to an immune challenge. I also found that perinatal morphine exposure also impacts the developing GABAergic system by altering expression of chloride cotransporters and GABA interneurons, resulting in altered function that manifests at the behavioral level in adulthood. Together, these studies attempt define the molecular underpinnings and long-term outcomes of perinatal opioid exposure and give rise to microglia as a potential therapeutic target in treating somatic withdrawal symptoms
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Blendy, Julie A. Committee members: Eisch, Amelia J.; Bennett, Frederick Chris; Shin Yim, Yeong
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247981947
- Access Restriction:
- Restricted for use by site license
The Penn Libraries is committed to describing library materials using current, accurate, and responsible language. If you discover outdated or inaccurate language, please fill out this feedback form to report it and suggest alternative language.